Youness Mokhtar's first-half goal saw Columbus edge Atlanta 1-0 in Group E at the Walt Disney World Resort in Florida on Tuesday.
Columbus will finish top of the group with three wins from as many games, while Atlanta are out.
Mokhtar's goal in the 18th minute came after a fine team move before the attacker tucked away a Milton Valenzuela pass.
Montreal overcame DC United 1-0 to remain a chance of progressing as one of the best third-placed teams.
Saphir Taider's deflected strike from distance just after the half-hour mark secured third place in Group C for Montreal.
While DC United have been eliminated, Thierry Henry's Montreal must wait for results in other games to see if they will feature in the last 16.
Penalties were needed following a 1-1 draw after the Crew's Gyasi Zardes struck 11 minutes from the end to cancel out Robin Lod's 18th-minute opener in Orlando, Florida on Tuesday.
Minnesota emerged triumphant on spot-kicks, converting all five of their attempts after Tyler Miller saved Chris Cadden's penalty.
San Jose Earthquakes await Minnesota in Friday's quarter-final showdown at Walt Disney World Resort.
In Tuesday's other last-16 fixture, the Timbers were 4-2 winners on penalties against Jaap Stam's FC Cincinnati.
Jaroslaw Niezgoda broke the deadlock for the Timbers when he coolly found the back of the net from inside the six-yard box after team-mate Sebastian Blanco was left unmarked before sliding a pass to the Polish forward.
But Cincinnati restored parity after Jurgen Locadia converted an 81st-minute penalty to force a shoot-out.
Portland, though, were not to be denied as Niezgoda scored the decisive penalty after Cincinnati's Kendall Waston missed and Locadia had his attempt saved.
The Timbers will go head-to-head with New York City for a place in the semi-finals on Friday.
Expansion side Charlotte drew a single-game attendance record of 74,479 fans, eclipsing the 73,019 mark set by Atlanta United in the 2018 MLS Cup.
Galaxy had the better of the chances with Victor Vazquez hitting the woodwork in the 18th minute, while Javier Hernandez forced a good save from Charlotte goalkeeper Kristijan Kahlina.
Alvarez made the decisive breakthrough with a spectacular left-foot shot from outside the box which nestled into the top corner to spoil the Charlotte party.
Scottish forward Lewis Morgan netted a first-half hat-trick as New York Red Bulls won 4-1 away to Toronto.
Morgan's finishes for his opening two goals were similar, set up by Patryk Klimala with curling right-foot shots in the 17th and 24th minutes.
Jesus Jimenez pulled one back for Toronto, before Klimala released Morgan on halfway and the Scot raced forward to slot home for his treble.
Carles Gil's penalty on the stroke of half-time earned 2021 Supporters' Shield winners New England Revolution a 1-0 home win over Dallas. The victory meant Revs head coach Bruce Arena became the all-time leader among MLS coaches for regular-season wins.
Francisco Calvo scored twice in the final 10 minutes as 10-man San Jose Earthquakes salvaged a 3-3 draw with Columbus Crew.
Ola Kamara netted a stoppage-time winner for DC United as they beat Cincinnati 1-0, while Chicago Fire and Orlando City drew 0-0 and Real Salt Lake won 1-0 over Seattle Sounders.
Colorado Rapids won 3-0 over Atlanta United at home and Vancouver Whitecaps held on for a goalless draw with reigning MLS Cup champions New York City.
Sporting KC got past Houston Dynamo 1-0 while 10-man Philadelphia Union edged Montreal 2-1 and Minnesota United drew 1-1 with Nashville.
David Beckham's Inter Miami were looking to keep their fading play-off hopes alive on Saturday, however, second-half goals from New York City pair Valentin Castellanos and Talles Magno dashed that dream.
Inter Miami had never taken a point against New York City in their three previous meetings, losing all three. New York City were one of two teams Inter Miami had faced more than once without claiming a point, along with DC United.
That drought continued despite Inter Miami defender Jorge Figal initially cancelling out Castellanos' 33rd-minute opener at DRV PNK Stadium, where co-owner Beckham was in attendance.
But New York City – third in the Eastern Conference – hit back via Castellanos and Magno to clinch a play-off spot thanks to results elsewhere as Inter Miami were left to pick up the pieces in Phil Neville's first season as head coach.
Cade Cowell, meanwhile, scored a memorable solo goal as the Earthquakes outlasted Real Salt Lake 4-3 in a wild showdown.
The 18-year-old collected the ball in his own half with 21 minutes remaining before barging down the right flank, cutting in between two RSL defenders and finishing past David Ochoa with the outside of his boot.
Elsewhere, Fabio netted a dramatic stoppage-time winner as New York Red Bulls edged Montreal 1-0 to move into the seventh and final play-off spot in the east.
Defending champions Columbus Crew kept their slim play-off hopes alive with a 3-1 win over DC United, Toronto and Atlanta United drew 1-1 and 10-man Dallas edged Austin 2-1.
With Tuesday's contest seemingly heading for a draw, Inter Miami's Makoun stepped up and scored a spot-kick in the 95th minute.
Unbeaten in six matches, Inter Miami – co-owned by former Manchester United, Real Madrid and England star Beckham – have won three consecutive matches for the first time in their history as they moved into the Eastern Conference play-off positions.
Toronto had just 15 points through 23 matches entering the matchup. Only five teams in MLS history have had fewer points at this stage of a season, most recently DC United in 2013 (13).
Kemar Lawrence was sent off in the 37th minute but Toronto thought they had snatched a winner with two minutes of regulation remaining when the hosts believed Jacob Shaffelburg's rebound crossed the line.
Inter Miami went up the other end and claimed all three points in the fifth minute of stoppage time – Makoun fouled by Chris Mavinga before tucking away the last-gasp penalty.
Following four consecutive clean sheets – a club first, Inter Miami are fifth in the east with 32 points from 23 rounds, while Toronto sit bottom after six straight defeats and nine games without a win.
Elsewhere, New York City and Dallas played out an entertaining 3-3 draw.
New York – fourth in the Eastern Conference – led 2-1 and 3-2 but had to settle for a point in a see-sawing contest at Red Bull Arena.
As for MLS champions Columbus Crew, they overcame New York Red Bulls 2-1 thanks to an 88th-minute goal via substitute Miguel Berry.
Columbus had lost six in a row and appeared on the verge of another defeat, trailing 2-1 at home after Isaac Atanga's 74th-minute goal gave Cincinnati the lead.
Berry had come on for Shaun Wright-Phillips a minute earlier, and he soon became the hero of the hour for the Crew.
The 23-year-old put home a rebound from a Pedro Santos shot in the 81st minute, then watched another rebound from an Alex Matan effort bounce off his chest and into the net less than two minutes later.
Columbus earned their first win since July 24 while Cincinnati saw their winless run extended to 11 (4L, 7D).
Montreal rolled to a 3-1 defeat of Toronto as the visitors were forced to play with 10 men for nearly the entire game.
Noble Okello picked up a straight red card after five minutes, condemning the visitors to a fourth straight defeat.
Samuel Piette, Joaquin Torres and Romell Quioto scored for Montreal, the latter two goals proving the difference after Ifunanyachi Achara had equalised for Toronto in the 58th minute.
Inter Miami earned a 0-0 draw at Orlando City thanks in part to Nick Marsman's first-half save of a Tesho Akindele penalty kick.
It was just the second clean sheet of the season for Phil Neville's side, while Orlando City are now unbeaten in six matches (2W, 4D).
In the first Los Angeles derby fixture of the MLS season, former Manchester United and Real Madrid star Chicharito guided the Galaxy to a 2-1 victory on Saturday.
Chicharito, who attempted just one shot in the loss to Seattle Sounders last time out, the sixth time in 10 MLS starts he has taken fewer than two shots (60 per cent) – he attempted fewer than two shots in just 36.7 per cent of his starts in the five major European leagues – improved his league-best tally to six goals with the 11th-minute opener at Dignity Health Sports Park, where he tucked the ball past Pablo Sisniega.
LAFC restored parity 28 minutes from the end when Diego Rossi equalised following some combination play between team-mates Latif Blessing and Corey Baird.
But the Galaxy walked away with maximum points after Chicharito teed up Jonathan dos Santos for the 79th-minute winner.
The Galaxy are second in the Western Conference, level on points with leaders San Jose Earthquakes, while LAFC are four points off the pace in eighth position.
Orlando City captain Nani stayed hot with another goal in the club's 1-1 draw against New York City.
Ex-United winger and Premier League champion Nani scored another memorable goal seven minutes into the second half, finding the back of the net with a stunning effort from the edge of the penalty area.
Nani's third goal in three games had Orlando on track for maximum points until a 77th-minute penalty via Valentin Castellanos salvaged a draw for the visitors.
"I've been working so hard and been focused on my games," Nani said post-match. "I think this is a reward [for] what you do during the week, the preparation into the games."
New York top the Eastern Conference on seven points, level with New England Revolution but a point clear of Orlando, New York Red Bulls and Nashville.
The Revolution lost 2-0 against Nashville, while the Red Bulls ran out 2-0 winners over Toronto.
Elsewhere, defending champions Columbus Crew defeated DC United 3-1, last season's Supporters' Shield winners Philadelphia Union topped Chicago Fire 2-0, Vancouver Whitecaps beat Montreal Impact by the same scoreline, Dallas and Houston Dynamo drew 1-1, while Colorado Rapids edged Minnesota United 3-2.
Sacha Kljestan netted a stoppage-time penalty to clinch all three points for Galaxy, who had been in a freefall with a winless nine-game span.
Chicharito poked in at the back post for the opening goal in the 62nd minute, pouncing on Larrys Mabiala's defensive error from Victor Vazquez's ball into the box.
The Timbers equalized 10 minutes later when Sebastian Blanco's cross-cum-shot drifted over Galaxy goalkeeper Jonathan Bond and in off the post.
Blanco hit the upright from a long-range effort, before LA won a penalty when substitute Efrain Alvarez was brought down inside the box by Josecarlos Van Rankin.
Kljestan fired low to Timbers keeper Steve Clark's right for the winner which moves Galaxy up to 42 points, retaining their grip on sixth spot in the Western Conference.
Supporters Shield-leading New England Revolution conceded late as they drew 2-2 at home with Chicago Fire.
The sides traded four goals in the second half, with Wilfred Kaptoum drilling in a low opener in the 47th minute before Alvaro Medran equalized instantly with a classy volley.
Gustavo Bou netted his 13th goal of the season to restore Revolution's lead with a deft lob from Carles Gil's lofted pass in behind the defence in the 76th minute.
Bou was denied by Chicago keeper Gabriel Slonina before Brian Gutierrez danced forward for the visitors, finding Ignacio Aliseda who fired home an angled 88th minute leveller.
Western Conference leaders Seattle Sounders missed the chance to close on New England after going down 2-1 at Houston Dynamo.
Maxi Urruti scored a spectacular volley to put Houston ahead on the quarter hour, with Darwin Quintero doubling their lead with a fine solo left-foot strike in the 20th minute.
Jimmy Medranda halved the deficit with a rifled 41st minute shot after recycling an over-hit corner, although Houston came closest to a second-half goal, hitting the woodwork four times, before Seattle's Joao Paulo had a stoppage-time free-kick cannon into the crossbar.
Real Salt Lake solidified their grip on a playoffs spot with a 3-1 home victory over Colorado Rapids, who are third in the Western Conference.
Minnesota United remained ahead of RSL by two points with a 1-0 triumph at lowly Austin thanks to Franco Frangapane's 16th-minute strike.
US international Gyasi Zardes netted a double as Columbus Crew thrashed Inter Miami 4-0, condemning them to their sixth straight defeat, during which they have scored one goal and conceded 16 times.
Luiz Araujo and Marcelino Moreno both netted late in each half as 10-man Atlanta United triumphed 2-0 at Toronto.
Junior Urso netted early as Orlando City eased past struggling Cincinnati 1-0, while DC United and Nashville drew 0-0 with the visitors recorded a draw for the fourth successive game.
Gyasi Zardes inspired Columbus in extra time of a 2-0 victory over Nashville.
The United States international's cutback found Pedro Santos to score the opener for the hosts in the 99th minute.
And, just four minutes later, Zardes sealed the win with a clinical finish in a one-on-one after being played in by Luis Diaz Espinoza.
Zardes has been directly involved in seven goals (five goals and two assists) in four matches against expansion sides over the past two MLS seasons, according to Opta.
It was enough for Columbus to reach the Eastern Conference finals for the second time in four seasons, and New England await.
After finishing eighth in the Eastern Conference, the Revolution beat Thierry Henry's Montreal Impact in the play-in round and stunned Philadelphia Union in the first round.
They continued their run with a 3-1 win over Orlando City on Sunday.
Carles Gil's 17th-minute penalty opened the scoring before Gustavo Bou made it 2-0.
Junior Urso pulled a scrappy goal back for Orlando after the half-hour mark, but their hopes of victory were hurt by Mauricio Pereyra's red card for a dangerous challenge in the 60th minute.
Still, Nani had a chance to equalise for Orlando in the 74th minute, only to see his penalty saved by Matt Turner.
The penalty save was just the second by a Revolution goalkeeper from the previous 23 on-target spot-kicks they had faced dating back to March 2016, according to Opta.
Instead, Bou got on the end of Gil's pass to poke in the sealer four minutes from time, sending New England to the Eastern Conference finals for the first time since 2014.
The 10-man Earthquakes held on for a 3-2 win over Los Angeles FC.
Latif Blessing tapped in the opener for LAFC midway through the first half, but an Eduard Atuesta own goal from a corner brought San Jose level.
Chris Wondolowski's side-footed finish from a Cristian Espinoza cross put the Earthquakes ahead eight minutes before half-time.
However, San Jose's chances took a hit when Jackson Yueill was sent off for a rash challenge in the 61st minute.
But Espinoza delivered an excellent finish to make it 3-1 and the Earthquakes held on despite Diego Rossi's late goal.
San Jose have earned 14 points from losing positions this season, including four come-from-behind wins, and both are the most in MLS in 2020, according to Opta.
Kellyn Acosta's 83rd-minute winner saw the Rapids edge the Portland Timbers 1-0 to reach the play-offs.
Acosta produced a fine finish into the top corner from inside the area after a pass from Diego Rubio to secure three points for Colorado.
It was just the Rapids' second MLS victory at Portland, ending a nine-match winless run dating back to 2011, according to Opta.
Colorado moved into the MLS play-offs for the first time since 2016.
Nani was sent off as Orlando City recorded a 2-1 victory over the Columbus Crew.
Chris Mueller had put Orlando ahead before Nani was harshly sent off for a sliding challenge.
Harrison Afful equalised for Columbus, but the 10-man Orlando found an 84th-minute winner through Benji Michel.
Orlando have won four straight matches against Columbus, the first time they have managed that against a single team in their MLS history.
Javier Hernandez scored but LA Galaxy were held to a 1-1 draw by the Seattle Sounders.
Hernandez's goal saw him end a 433-minute scoring drought dating back to July.
Elsewhere, Dallas beat Nashville 1-0 and Minnesota United and the Chicago Fire drew 2-2.
Eastern Conference leaders Columbus produced a late comeback to draw with Chicago Fire, but their lead is now just three points after Philadelphia enjoyed a win.
Philadelphia left it late to overcome New England Revolution 2-1 at Subaru Park.
With the game locked at 0-0, New England were reduced to 10 men when Matt Polster was shown a second yellow card in the 56th minute.
Just 17 minutes later and Philadelphia took the lead, Anthony Fontana chipping in from close range.
But a fine equaliser from Tajon Buchanan appeared to have New England set to earn a point.
However, there was late drama as Fontana drilled in a wonderful goal from 25 yards in the 95th minute.
Columbus appeared set for their second defeat of the MLS season when they fell 2-0 behind in Chicago.
But Fatai Alashe pulled a goal back for the Crew before Gyasi Zardes' 88th-minute equaliser.
At the bottom of the conference, Inter Miami slumped to a 2-1 loss to Orlando City.
Coming off a win over Atlanta United, Inter suffered their seventh loss in 11 games this season.
Elsewhere, the New York Red Bulls recorded a 2-0 win over DC United and New York City edged Cincinnati 2-1.
Nashville enjoyed a 4-2 win over Atlanta United, Dallas beat Houston Dynamo 2-1 and the Colorado Rapids thrashed Real Salt Lake 5-0.
Galaxy, who had endured a nine-game winless skid, had beaten Portland Timbers 2-1 on the weekend before backing that up in Houston to reinforce their grip on sixth spot in the Western Conference midweek.
Greg Vanney's Galaxy went ahead in the 39th minute from veteran Sacha Kljestan's penalty, after Maynor Figueroa brought down Kevin Cabral inside the box.
Zarek Valentin's own goal on the stroke of half-time from Efrain Alvarez's cutback doubled Galaxy's advantage.
Two minutes into the second half, Javier 'Chicharito' Hernandez provided a well-weighted pass for Kevin Cabral to add a third, moving Galaxy up to 45 points and above Real Salt Lake into fifth in the west.
New England Revolution moved another step closer to clinching the Supporters' Shield with a come-from-behind 3-2 win at DC United.
Adam Buksa, Carles Gil and Gustavo Bou all scored within 18 minutes as the Revolution responded to Nigel Robertha's 51st-minute opener for DC United.
The result moved Eastern Conference pacesetters New England to 69 points from 31 games, with Western Conference leaders Seattle Sounders closest behind them on 58 points after 30 games after they lost ground following a 1-1 draw with third-placed Colorado Rapids.
Elsewhere, Nashville – second behind New England in the east – drew for the fifth straight game in a 1-1 stalemate against defending MLS champions Columbus Crew and Cristian Arango's hat-trick guided Los Angeles FC past Dallas 3-2.
Inter Miami snapped their six-game losing skid and kept alive their faint play-off aspirations with a 3-0 home victory over Toronto.
Gudmundur Thorarinsson equalised late for New York City but their winless run extended to six games after a 1-1 draw at Atlanta United, Minnesota United were 3-2 winners against Philadelphia Union, Orlando City and Montreal played out a 1-1 draw.
Chicago Fire prevailed 4-3 over struggling FC Cincinnati, Vancouver Whitecaps came from two goals down to win 3-2 away to Portland Timbers, while San Jose Earthquakes eased past lowly Austin 4-0.
The Revolution raced to a three-goal lead but were forced to hold on in the final quarter of an hour after strikes from Patryk Klimala and Andres Reyes midweek.
Carles Gil provided the assist for all three Revolution goals, taking his season tally to an MLS-high 10, stabbing through to Canadian forward Tajon Buchanan for the 26th-minute opener.
Spanish midfielder Gil laid off for DeJuan Jones' 32nd-minute strike, before pumping the ball forward for Gustavo Bou to make it 3-0 six minutes into the second half before the Red Bulls rallied.
The win moved New England five points clear in the Eastern Conference, sitting ahead of Orlando City – who have a game in hand – and Philadelphia Union who are both on 18 points.
Jamiro Monteiro scored the only goal of the game as Philadelphia kept up their good form with a 1-0 victory over Columbus Crew.
Seattle Sounders remain unbeaten after Raul Ruidiaz's 88th-minute penalty clinched a 2-1 win against Real Salt Lake, extending their club-record unbeaten start to 10 matches.
Cristian Roldan had put Seattle ahead five minutes into the second half, reacting fastest to score from a rebound inside the box.
RSL levelled with 12 minutes to go, when they won a penalty which was converted by Slovakian Albert Rusnak.
Ruidiaz had the final say netting his eighth goal of the season with a cool Panenka finish from the spot for the Western Conference-leading Sounders.
New York City continued their rollercoaster run with a 1-0 triumph over Atlanta United via Ismael Tajouri's 69th-minute winner.
Javier 'Chicharito' Hernandez got on the scoresheet before late drama as LA Galaxy won 2-1 at Vancouver Whitecaps.
Former Manchester United and Real Madrid forward Chicharito opened the scoring, sliding home in the 47th minute with Galaxy appearing destined to claim all three points before a 90th-minute equaliser from Janio Bikel.
There would be another late twist, when the Galaxy's Efrain Alvarez scored in the third minute of stoppage – his stunning strike finding the back of the net after hopeful ball into the box.
Mexico international Carlos Vela also netted along with providing an assist as Los Angeles FC won 2-0 over Dallas.
Elsewhere, Sporting Kansas City defeated Colorado Rapids 3-1, Portland Timbers and Houston Dynamo drew 2-2, Nashville outlasted Toronto 3-2 courtesy of a 92nd-minute winner, Cincinnati edged Chicago Fire 1-0, Minnesota United beat Austin 2-0, while 10-man Montreal and DC United played out a goalless stalemate.
Higuain struck the winner in the 16th minute for Inter who have claimed 13 points from their past five matches to surge up to ninth in the Eastern Conference.
Inter had endured a six-game losing span in May and June but Phil Neville's side have bounced back, losing only once in their past 10.
The former Real Madrid forward swooped on a wayward back pass from Josh Williams, taking a touch inside the box and dinking a shot over Crew keeper Eloy Room, with Vito Wormgoor unable to clear it on the line.
New England maintained their stronghold on the lead at the top of the table with a come-from-behind 2-1 win over 10-man New York City.
Santiago Rodriguez had put City ahead with an 11th-minute volley before Revolution midfielder Emmanuel Boateng drive in a low leveller 10 minutes later. Tom McNamara may have put New England ahead when he hit the post late in the half.
Alfredo Morales was sent off for a second bookable offence, an heavy tackle on McNamara, early in the second half.
New England capitalized with in-form Tajon Buchanan coming up with a 65th minute winner from Carles Gil's assist.
Nashville maintained their strong season with a 1-0 victory on the road over Montreal after Walker Zimmerman's glancing 66th-minute header, keeping them second in the Eastern Conference behind New England.
Sporting KC struck twice inside the first 10 minutes from Jose Mauri and Johnny Russell as they won 2-0 over Chicago Fire to stay in touch with Western Conference leaders Seattle Sounders.
Colorado Rapids squandered an opportunity to temporarily go top in the west after Samuel Grandsir's late equalizer for LA Galaxy in a 1-1 draw. The Rapids instead slip to third below KC.
Seattle Sounders remained first in the west with a 1-0 home win over Minnesota United thanks to Joao Paulo's 22nd-minute strike.
Teenage sensation Ricardo Pepi scored his 12th goal of the season as Dallas drew 1-1 with San Jose Earthquakes, while lowly Houston Dynamo won 3-0 over fellow Texas outfit Austin.
New York Red Bulls continue to struggle for wins, only managing a 1-1 home draw with DC United after a controversial penalty award for a Sean Nealis handball.
Cincinnati snapped their three-game losing run with a 2-0 home win over struggling Toronto, who have lost five in a row.
Higuain converted an 81st-minute free-kick and it proved to be the winner as Inter Miami defeated New York Red Bulls 2-1 on Wednesday.
The former Argentina international, who joined David Beckham's Inter Miami from Serie A champions Juventus, missed a penalty on debut last month.
In his third appearance for Inter Miami, Higuain earned a free-kick with nine minutes remaining and stepped up to beat Red Bulls goalkeeper David Jensen with a powerful shot into the top corner.
Higuain's first MLS goal came via a direct free-kick after not scoring a set-piece in 428 matches during his time in the top five European leagues, per Opta.
"That's my role," Higuain said in a post-match news conference. "I've been playing in the best leagues in the world and that's my main function, to score."
The Red Bulls had led through Omir Fernandez's 53rd-minute opener, before Matias Pellegrini equalised two minutes later in New Jersey.
Inter Miami are 12th in the 14-team Eastern Conference with 14 points from 16 games, while the Red Bulls are six points better off in seventh.
The visiting Timbers defeated the struggling Galaxy in a wild nine-goal showdown in Carson, California.
Portland led 2-1 at half-time before scoring another four goals in a thrilling encounter at Dignity Health Sports Park.
Felipe Mora and Jeremy Ebobisse each finished with braces as the Timbers scored a joint-club record six goals for the second time in four matches, having not scored more than five times in any of their first 337 MLS matches, via Opta.
The Galaxy have lost five matches in a row to sit bottom of the Western Conference, while the Timbers are second and three points adrift of leaders Seattle Sounders – who edged Real Salt Lake 2-1.
Elsewhere, New York City eased past DC United 4-1, Eastern Conference leaders Toronto downed New England Revolution 1-0 and Philadelphia Union were too good for FC Cincinnati 3-0.
Dallas lost 2-0 to Houston Dynamo, Sporting Kansas City were 1-0 winners over Chicago Fire, San Jose Earthquakes beat nine-man Vancouver Whitecaps 3-0, Montreal Impact topped Columbus Crew 2-1, while Atlanta United and Orlando City played out a goalless draw.
The Colorado Rapids-Los Angeles FC clash was postponed after one new confirmed case of coronavirus among the Rapids staff.
Galaxy stretched their winning streak to four games with a 3-0 victory in the derby clash at Dignity Health Sports Park on Sunday.
Cristian Pavon opened the scoring in the 51st minute, lobbing Pablo Sisniega after the LAFC goalkeeper was left stranded having come to attempt to collect an Emiliano Insua pass.
Just two minutes later and LAFC were dealt another blow, Mark-Anthony Kaye sent off for a rash challenge on Julian Araujo.
Galaxy capitalised on their numerical advantage as Sebastian Lletget tucked away a smart Pavon set-piece in the 73rd minute.
And 10 minutes later Lletget sealed the win, his overhead kick from Rolf Feltscher's cross finding the corner.
Galaxy jumped into fourth in the Western Conference after a second straight El Trafico win.
Columbus are five points clear atop the Eastern Conference after a 3-0 win over FC Cincinnati.
The Crew needed until the second half to break the game open at MAPFRE Stadium in Ohio.
Pedro Santos opened the scoring in the 52nd minute before Gyasi Zardes' brace.
Zardes got on the end of a Santos cross before later scrambling in to see Columbus to a seventh win in 10 MLS games this season.
Philadelphia Union are second to Columbus and recorded a 3-0 win over New York Red Bulls.
Minnesota United scored four second-half goals in a 4-0 win over Real Salt Lake, New England Revolution edged Chicago Fire 2-1 and Portland Timbers recorded a 2-1 victory against Seattle Sounders.
Inter Miami's struggles continued with a 0-0 draw against Nashville as former Juventus and Paris Saint-Germain midfielder Blaise Matuidi made his debut, while DC United and New York City also drew 0-0.
Coming off a defeat to Los Angeles FC, Inter Miami went down to DC United 2-1 on Saturday.
Rodolfo Pizarro scored the first MLS goal in the club's history, sweeping in a Lewis Morgan cross to give them the lead in just the second minute.
However, the game turned early in the second half when, after Morgan thought he had doubled his side's lead, the visitors had the goal ruled out and Roman Torres sent off for a handball.
DC equalised through Yamil Asad's penalty in the 59th minute before finding what proved to be the winner just after the hour-mark.
Edison Flores hit the post with a free-kick and Frederic Brillant reacted quickest to fire in the rebound and lift DC to their first win of the season.
LA Galaxy are without a win through two games after suffering a 1-0 loss at home to the Vancouver Whitecaps.
Tosaint Ricketts' smart side-footed finish in the 74th minute was enough for the Whitecaps.
Joe Corona was then sent off for Galaxy, who were beaten despite David Bingham later saving a Lucas Cavallini penalty.
Without the injured Josef Martinez, Atlanta United made it two wins from two by beating Cincinnati 2-1.
There are three teams with perfect records in the Western Conference in Sporting Kansas City, Minnesota United and the Colorado Rapids.
Sporting KC thrashed Houston Dynamo 4-0, Ike Opara netted a brace in Minnesota's 5-2 win over the San Jose Earthquakes and Colorado edged Orlando City 2-1 thanks to Drew Moor's late winner.
New England Revolution and Chicago Fire drew 1-1, Real Salt Lake came from behind to hold the New York Red Bulls to a 1-1 draw and Maximiliano Urruti's brace helped Montreal Impact draw 2-2 with Dallas.
Ifunanyachi Achara's goal on his MLS debut saw Toronto overcome New York City 1-0, while the Seattle Sounders drew 1-1 against Columbus Crew.
In their first season in MLS, Inter Miami reached the play-offs after a 2-1 win over FC Cincinnati on Decision Day.
Mikey Ambrose's 25-yard strike in the 19th minute gave Diego Alonso's side the lead before Leandro Gonzalez Pirez doubled the advantage with a header.
Joe Gyau's brilliant goal halved the deficit for Cincinnati in the 66th minute, but Inter Miami held on despite Andres Reyes' red card.
Philadelphia won the first trophy in their history, securing the Supporters' Shield thanks to a 2-0 win over New England Revolution.
Sergio Santos and Cory Burke scored either side of half-time for the Union, who finished three points clear of Toronto atop the Eastern Conference.
Philadelphia won all nine of their home matches during the 2020 MLS season, tied for the second-longest single-season home winning streak in league history.
Toronto were chasing Philadelphia but fell to a 2-1 loss to New York Red Bulls.
Montreal Impact also secured a play-off place thanks to a come-from-behind 3-2 win over DC United.
DC led twice as Donovan Pines and Ola Kamara had goals cancelled out by Bojan Krkic and Victor Wanyama respectively.
But Romell Quioto tapped in an 88th-minute winner for the Impact, who had Samuel Piette sent off in additional time.
New York City edged Chicago Fire 4-3 in a thriller, Columbus Crew overcame Atlanta United 2-1 and Nashville beat Orlando City 3-2.
Sporting Kansas City wrapped up the top seed in the Western Conference after a 2-0 win over Real Salt Lake.
It meant the Seattle Sounders' 4-1 victory against San Jose Earthquakes mattered little as they finished second.
Carlos Vela scored in Los Angeles FC's 1-1 draw with Portland Timbers, Minnesota United cruised past Dallas 3-0, Colorado Rapids beat Houston Dynamo 2-1 and Vancouver Whitecaps handed a 10-man LA Galaxy a 3-0 loss.
City defender Alexander Callens netted the game's only goal in the 29th minute, while goalkeeper Sean Johnson was outstanding for the visitors.
Callens powered in the winner with a bouncing header from Santiago Rodriguez's corner.
Minnesota almost equalised in the 90th minute but were thwarted by a spectacular double save by Johnson from Emanuel Reynoso and Robin Lod efforts.
City moved ahead of Philadelphia Union in the east, after they could only manage a 1-1 draw away to under-achieving New England Revolution.
The Revs, who won last season's Supporters' Shield, have rallied after a poor start to their campaign, going unbeaten in their past five, but have only collected 16 points from 13 games.
Gustavo Bou had put New England ahead from the penalty spot in the 75th minute, but Union levelled two minutes later after Omar Gonzalez's inexplicable error allowed Mikael Uhre to score.
Montreal, who are third in the east, got back on the winners' list with a hard-fought 4-3 victory over Cincinnati with a double from Rommel Quioto.
Luquinhas netted a brace as New York Red Bulls stayed in touch with the Eastern Conference's top three with a 4-1 home victory over struggling DC United.
In the Western Conference, LAFC remains four points clear at the top after Brian Rodriguez's 47th-minute winner clinched a 3-2 triumph over San Jose Earthquakes.
LAFC had raced to a 2-0 lead inside 13 minutes but San Jose equalised after two goals from in-form Jeremy Ebobisse, who has scored an equal-league high nine times this term.
Rodriguez, who got the assist for Ryan Hollingshead's 13th minute goal, scored when a loose ball arrived at his feet unmarked at the back post, firing past Earthquakes goalkeeper JT Marcinkowski.
Nashville ended the Colorado Rapids' remarkable 23-game unbeaten run at home with a 3-1 victory.
Charles Sapong netted in the eighth minute, before Hany Mukhtar's quickfire double had Nashville 3-0 up inside 18 minutes. The win moves Nashville up to fifth in the west.
Dallas came from behind to win 3-1 at Orlando City, Real Salt Lake won their third straight with a 3-0 victory over Houston Dynamo and Vancouver Whitecaps moved off bottom spot with a 1-0 triumph at Sporting KC.
Inter Miami extended their unbeaten run to four games with a 2-1 home win over Portland Timbers, Columbus Crew triumphed 2-1 over 10-man Atlanta United and Toronto won 3-2 over Chicago Fire after two late Pozuelo goals.
Former Manchester United winger Nani had set up Daryl Dike for a 26th-minute opener with a tackle-cum-pass before Silvester van der Water doubled Orlando's lead three minutes later with a cross which eluded everyone.
But the visitors rallied after the break with a double strike inside three minutes, firstly with Antonio Carlos' 52nd-minute own goal.
Minutes later Lucas Zelarayan picked out Derrick Etienne Jr who cushioned a pass into the box for Miguel Berry to equalize.
Orlando grabbed all three points with Dike laying back a pass for Junior Urso to lash home a 69th-minute winner from the edge of the box.
The result moves Orlando above Nashville into second spot in the east with 38 points from 22 games, having gone six games unbeaten in the MLS.
Inter Miami continued their excellent recent form after Brek Shea's 90th-minute winner earned them a 1-0 victory away to Cincinnati.
The result extends Phil Neville's side's unbeaten run to four games and means they have lost only once in their past nine, climbing up to 10th spot in the east.
Dominique Badji also netted a late winner, scoring in the 89th minute to lift the Colorado Rapids into second in the west with a 1-0 victory at San Jose Earthquakes.
Real Salt Lake came from a goal down early to win 3-2 over Dallas, while Vancouver Whitecaps scored twice in the final 20 minutes to beat struggling Austin 2-1.
