A 2-1 victory over the Chicago Fire saw Philadelphia push three points clear of Toronto in the Eastern Conference, and for the Supporters' Shield, which they are bidding to win for the first time.
Kacper Przybylko opened the scoring from the penalty spot approaching the half-hour mark, following a handball in the area.
Chicago's chances of a comeback were dealt a blow nine minutes before half-time, Francisco Calvo sent off after a tackle on Alejandro Bedoya.
However, they managed to find an equaliser prior to the break as Robert Beric headed in from close range.
But Philadelphia scored what proved to be the winner in the 65th minute, when Cory Burke headed in a cross from Olivier Mbaizo.
According to Opta, Union became the first team to win their first eight home matches of an MLS season since San Jose in 2002, when the Earthquakes claimed their first 10.
The Timbers clinched a spot in the play-offs thanks to a 5-2 thrashing of the struggling LA Galaxy.
Jaroslaw Niezgoda scored a brace for Portland, who were 3-0 up after 30 minutes following Diego Valeri's penalty.
Eryk Williamson and Andy Polo also netted as the Timbers thrashed the Galaxy, who are bottom of the Western Conference.
Portland became the first team with multiple five-goal games against an opponent in a single MLS season since the Fire against the New York Red Bulls in 2008, having thrashed the Galaxy 6-3 earlier this month.
Chris Wondolowski scored a brace as the Earthquakes enjoyed a 2-0 win over Real Salt Lake.
It was his 24th multi-goal game in MLS. Only Landon Donovan (32) has more.
The New York Red Bulls left it late to edge the New England Revolution 1-0 and reach the play-offs, Sporting Kansas City overcame Cincinnati 1-0 and Orlando City thrashed Atlanta United 4-1.
New York City upset Toronto 1-0, Minnesota United beat the Colorado Rapids 2-1, DC United were too good for Columbus Crew 1-0, Dallas claimed a 2-1 win over Inter Miami and Los Angeles FC were 2-1 victors over the Houston Dynamo to clinch their play-off place.
Union scored first-half goals from Alejandro Bedoya and Daniel Gazdag, while Sergio Santos had a goal disallowed on the stroke of half-time, as Philadelphia got some revenge after last season's Eastern Conference final defeat to City.
Bedoya put Philadelphia ahead in the 12th minute, but City thought they had an avenue back into the game when referee Ted Unkel awarded them a penalty and sent off Jack Elliott for a 28th-minute last-man push on Santiago Rodriguez.
However, VAR intervened and determined that Rodriguez had illegally used his hand in the lead-up, meaning the penalty and red card were overturned.
The win was Philadephia's first at Yankee Stadium and came despite City bossing the possession count with 74 percent.
Former Liverpool and Bayern Munich attacker Xherdan Shaqiri netted his first MLS goal as Chicago Fire won 3-1 over Sporting KC.
Shaqiri scored from the spot in the 50th minute to make it 2-0 as Chicago extended its unbeaten start to the new season with Kacper Przybylko hitting a double.
Jesus Ferreira scored a first-half hat-trick as Dallas defeated Portland Timbers 4-1 in a sign of intent for the forward ahead of USA's upcoming World Cup qualifiers.
All three of Ferreira's goals came in a 10-minute span, marking his first-ever MLS hat-trick.
Gonzalo Higuain scored, but Inter Miami remain winless this term after a 3-1 loss away to last season's strugglers Cincinnati.
The result leaves Phil Neville's side with an MLS-worst record of one point from four games, having conceded 10 goals and only scored two.
Karol Swiderski netted a double as Charlotte upset New England Revolution 3-1, while Luis Amarilla's 32nd-minute strike lifted Western Conference leaders Minnesota United past San Jose Earthquakes 1-0.
Tyler Pasher's 90th minute goal salvaged a 1-1 home draw for Houston Dynamo against Colorado Rapids, while 10-man Atlanta United scored twice in the final five minutes to rescue a 3-3 draw with Montreal.
Facundo Torres' early goal got Orlando City past LA Galaxy 1-0, Bob Bradley's Toronto knocked off DC United 2-1 and Real Salt Lake edge 10-man Nashville 2-1.
Javier 'Chicharito' Hernandez scored twice for the Galaxy in a 3-3 draw with Minnesota United on Decision Day, but RSL's last-gasp 1-0 win over Sporting Kansas City changed the landscape of the Western Conference.
RSL pipped the Galaxy – without post-season football for the second straight campaign – to the seventh and final play-off spot on victories for the season via a 95th-minute winner, having finished level on 48 points at the end of 34 rounds.
Minnesota finished fifth to clinch a post-season berth in the west, along with sixth-placed Vancouver Whitecaps, who drew 1-1 against Seattle Sounders.
Seattle's stalemate and Sporting KC's late loss allowed Colorado Rapids to secure top seed in the Western Conference following a 5-2 rout of Los Angeles FC, who were eliminated as a result.
In the Eastern Conference, Orlando City beat Montreal 2-0 for a spot in the play-offs, along with Atlanta United (2-1 over FC Cincinnati) and New York Red Bulls – the latter using a 1-1 draw against Nashville to extend their post-season streak to 12 years.
Supporters' Shield winners New England Revolution lost 1-0 to already eliminated Inter Miami, Portland Timbers eased past lowly Austin 3-0, DC United defeated Toronto 3-1, 10-man New York City drew 1-1 with Philadelphia Union and reigning champions Columbus Crew – who will not defend their title – beat Chicago Fire 2-0.
Chris Wondolowski scored in the San Jose Earthquakes' 1-1 draw against Dallas before the league's all-time leading scorer announced his retirement.
Fabio scored the 79th-minute winner, his second goal of the season, after Coronel had saved Mauricio Pereyra's penalty on the stroke of half-time.
Venezuelan midfielder Cristian Casseres fired in an excellent left-foot strike to open the scoring in the sixth minute but Orlando had a chance to level moments before half-time.
Uruguayan midfielder Pereyra shot low to Coronel's left but the Brazilian dived well and palmed away the spot-kick.
Pereyra partly made up for his miss, laying off the pass for Chris Mueller to equalize high into the back of the net in the 59th minute.
But Fabio held off a defender to fire home to secure the Red Bulls' first road win of the season, moving them up to seventh in the Eastern Conference.
DC United had seven different scorers as they trounced Toronto 7-1, keeping them ahead of the Red Bulls in sixth in the East.
Andy Najar, who did not score one of United's goals, set up two and was named Player of the Match.
Eastern Conference leaders New England Revolution blew a two-goal lead to draw 2-2 away to Columbus Crew.
Goals from Tajon Buchanan and Gustavo Bou had New England on the path to victory but Columbus fought back with Andrew Farrell's comical own goal levelling it up.
LAFC grabbed their maiden road win of the campaign, edging Real Salt Lake 1-0 after Jose Cifuentes' 69th-minute strike from Eddie Segura's pass.
Segura was the hero moments later with a diving goal-line clearance to deny Rubio Mendez's on-target lob.
Houston Dynamo and Cincinnati traded goals inside the opening five minutes in a 1-1 draw. Houston have drawn four games in a row.
Argentine forward Ignacio Aliseda scored twice as Chicago Fire claimed their second win of the season, triumphing 3-0 over Atlanta United.
Inter Miami's struggles continued with a 1-0 defeat away to Montreal. Miami have only managed eight points from 11 games, losing their past five.
Benjamin Kikanovic scored late to earn a 2-2 draw for struggling San Jose Earthquakes at Minnesota United. The Earthquakes are winless in eight.
Charles Sapong's second-minute goal was enough for Nashville to secure a 1-0 home win over fellow Eastern Conference contenders Philadelphia Union.
Clark – aged 17 years, four months and 18 days – became the youngest player to score in his first two MLS appearances on Wednesday, per Opta.
Hours after joining the Red Bulls, Clark capped his debut with a goal in Saturday's 1-0 win over Atlanta United.
Clark became the youngest player to score his maiden goal for the Red Bulls since Jozy Altidore in 2006.
He continued where he left off against Toronto, netting the equaliser with 13 minutes remaining midweek.
Following Alejandro Pozuelo's 23rd-minute penalty, Clark earned the visiting Red Bulls a point by firing a shot into the top corner of the net from outside the box.
The Red Bulls are seventh in the Eastern Conference, while Toronto – already play-off bound – remain top through 18 games.
Elsewhere, reigning Supporters' Shield holders Los Angeles FC and struggling LA Galaxy were beaten.
Lucas Cavallini's brace lifted Vancouver Whitecaps to a 2-1 victory against fourth-placed LAFC.
Canada international Cavallini has now scored in back-to-back games after finding the net just twice in his first 11 MLS matches for the Whitecaps, who climbed up to eighth in the standings and in the play-off positions.
As for the Western Conference's bottom side – the Galaxy – they were swept aside 4-0 by San Jose Earthquakes in the Cali Clasico.
Former Manchester United and Real Madrid striker Javier Hernandez was substituted early in the second half, with the Galaxy only managing four goals in the 652 minutes 'Chicharito' has been on the pitch this season.
It was a sixth consecutive defeat for the slumping Galaxy as the Earthquakes moved within a point of LAFC in the west.
Wednesday's scheduled Minnesota United-Chicago Fire fixture was postponed due to a suspected coronavirus case among Minnesota's team delegation.
In other results, New England Revolution edged Montreal Impact 3-2, FC Cincinnati were 2-1 winners over Columbus Crew, Orlando City and New York City drew 1-1, Atlanta saved a 1-1 draw at Inter Miami, Sporting Kansas City fell 1-0 to Dallas, DC United and Philadelphia Union shared the points in a four-goal clash, Real Salt Lake trumped Portland Timbers 2-1 and Nashville accounted for Houston Dynamo 3-1.
Adam Buksa's goal after 70 minutes kept New England atop the east with a 1-0 win over FC Cincinnati.
The Revolution are now five points clear of second-placed Orlando City after the Lions' 2-1 defeat to New York Red Bulls.
Ten-man New York City FC stunned Los Angeles FC 2-1 on Ismael Tajouri-Shradi's 90th minute goal after Jesus Medina had equalised 20 minutes earlier.
Trailing 2-0 heading into the final 10 minutes, Nashville saw Hany Mukhtar score in the 80th and 83rd minutes to lift the visitors to a 2-2 draw with Atlanta United.
Mason Toye's 87th-minute strike gave Montreal a 1-0 victory over Chicago Fire, while Columbus Crew held on to beat Toronto FC 2-1 on early goals by Luis Diaz and Gyasi Zardes.
Sporting Kansas City rallied from a first-half deficiit to defeat Houston Dynamo 3-2 as Gianluca Busio, who turned 19 on Friday, started the comeback with an outrageous free kick.
Ola Kamara's brace led the way as D.C. United rolled 3-0 to keep Inter Miami winless at home.
A late own goal from Tanner Beason of the San Jose Earthquakes gave LA Galaxy a 1-0 win.
Niko Hansen's 78th-minute tally salvaged a 1-1 draw for Minnesota United against Real Salt Lake after Damir Kreilach opened the scoring in the 13th minute.
Colorado Rapids got goals from Keegan Rosenberry, Tanner Tessmann and Michael Barrios to ease past last-place FC Dallas 3-0.
Thomas McNamara's goal in the 88th minute gave New England a 3-2 victory over New York City FC, just three minutes after Ismael Tajouri-Shradi had equalised for the home side.
Gustavo Bou and Jon Bell also found the net for the Revolution, who are five points clear of Orlando City in the Eastern Conference.
Out west, goals four minutes on either side of half-time from Yeimar Gomez and Raul Ruidiaz lifted unbeaten Seattle to a 2-1 win at LA Galaxy.
Orlando City got early goals from Tesho Akindele and Nani before Junior Urso netted in the 84th minute to defeat Toronto FC 3-2.
Columbus Crew got a brace from Gyasi Zardes to beat Chicago Fire 2-0, while Colorado Rapids won by the same scoreline at FC Cincinnati as Diego Rubio and Jonathan Lewis found the scoresheet.
Ola Kamara's 72nd-minute penalty was the difference for D.C. United in a 1-0 win over Inter Miami, who saw Gregore and Ryan Shawcross shown red cards.
Portland Timbers defeated Sporting Kansas City 2-1 on first-half goals from Dairon Asprilla and Marvin Loria.
Ricardo Pepi's 68th-minute equaliser gave FC Dallas a 1-1 draw with Minnesota United after Franco Fragapane had given the visitors a first-half lead, while Austin FC and San Jose Earthquakes finished in a 0-0 draw.
Houston Dynamo earned a point on the road in a 1-1 draw against Los Angeles FC as Maximiliano Urruti matched Jose Cifuentes' second-half goal.
Bou struck at the death in the play-in match at Gillette Stadium, where the Revolution earned a date with Philadelphia Union in the opening round of the MLS Cup play-offs.
The Argentine forward's goal came on his eighth shot of the match, the most by a Revolution player in a play-off match in club history, per Opta.
Bou's match-winning effort – officially timed at 94 minutes, 37 seconds – is New England's latest winning goal since Kelyn Rowe at 95:47 in 2017.
The tie was level after Montreal's Romell Quioto cancelled out Carles Gil's 38th-minute opener just past the hour mark – the Impact scoring in 21 consecutive away matches (including play-off games), the longest streak in MLS history.
In the day's other play-in fixture, Nashville eased past David Beckham's Inter Miami 3-0.
In a battle of the 2020 expansion sides, Nashville progressed to face Toronto thanks to goals from Randall Leal, Hany Mukhtar and Dax McCarty.
A two-goal first half, fuelled by Leal and Mukhtar, set the tone as Nashville became the first true expansion team to win a play-off match since Chicago Fire in 1998, according to Opta.
Supporters' Shield leaders the Revolution booked their play-off spot courtesy of a 90th-minute winner from MVP candidate Carles Gil on Wednesday.
New England – 15 points clear atop the Eastern Conference and 10 points ahead in the Supporters' Shield race – entered the midweek clash amid a four-match unbeaten streak against Chicago – the Revolution's longest undefeated run versus the Fire.
They extended that streak in an entertaining showdown with hosts the Fire at Soldier Field in Chicago.
Henry Kessler opened the scoring for the Revs in the 11th minute before Chicago's Carlos Teran restored parity entering the interval.
The Revs and Fire traded goals via Teal Bunbury and Gaston Gimenez before substitute Gil struck at the death.
Nashville, who are second to New England in the east, crushed David Beckham's Inter Miami 5-1.
Inter Miami's club-record six-match unbeaten streak (W5 D1) ended with a 4-0 rout at the hands of New York Red Bulls last time out – it was only the club's second defeat in 12 matches following a six-game losing run.
But Inter Miami crashed to consecutive humiliating defeats in a match that saw Gregore sent off with four minutes of regulation remaining.
Hany Mukhtar's brace fuelled visiting Nashville, with Inter Miami ninth in the Eastern Conference and three points adrift of the play-off positions.
Meanwhile, the derby honours were shared between the Red Bulls and 10-man New York City following a dramatic 1-1 draw.
Patryk Klimala converted a 102nd-minute penalty to salvage a point for the Red Bulls.
Reynoso scored twice inside the opening 20 minutes to set up the triumph which lifts United up to sixth spot after they had suffered back-to-back defeats.
The Argentine fired in a low left-foot shot to open the scoring in the fourth minute before jinking inside and netting from similar range in the 20th minute to double the lead.
United goalkeeper Tyler Miller saved well to deny Dejan Joveljic prior to half-time, before Ethan Finlay got in behind the Galaxy defence from Franco Frangapane's pass to add a third in the 66th minute.
The result sees Minnesota move up to sixth in the Western Conference with 34 points, while Galaxy stay fourth but are winless from their past six games.
Runaway league leaders New England were held to a 1-1 home draw with Columbus Crew.
Polish attacker Adam Buksa netted a 62nd minute equalizer after US international Gyasi Zardes had put Crew ahead in the 58th minute.
Zardes had missed a gilt-edged header in the 22nd minute but he took his opportunity early in the second half from Harrison Afful's cross.
Buksa levelled, swooping on a poor Jonathan Mensah pass in defence, handing the Pole a sniff on goal which he converted with a left-foot shot.
An injured Eloy Room made two crucial late saves to deny Buksa a winner as the Crew held on.
Struggling Austin slumped to a fifth straight defeat after blowing a 3-1 second-half lead to lose 4-3 to San Jose Earthquakes.
The Earthquakes scored three goals in 14 second-half minutes to complete the comeback headlined by Javier Lopez's double.
New York City firmed up their grip on a playoffs spot after a 2-1 win away to Cincinnati who were reduced to nine men after red cards to Alvaro Barreal and Isaac Atanga.
Damir Kreilach's early second-half goal was enough to get Real Salt Lake past Seattle Sounders 1-0, while Houston Dynamo won 3-2 over Dallas in the Texas derby.
Lowly Toronto ended their six-game losing run with a shock 2-1 home win over Nashville, while Atlanta United secured their third straight triumph with a 3-2 victory over DC United.
Cristian Roldan inspired Seattle to a 3-1 win over the Galaxy in California.
Roldan opened the scoring in the 12th minute, completing a fine team move by getting on the end of a Jordan Morris cross.
Morris doubled the lead seven minutes before half-time, finishing after a lovely pass from Nicolas Lodeiro.
Roldan produced a clinical finish from a Joao Paulo pass to make it 3-0 just after the hour-mark, with Seattle winning despite Sebastian Lletget's late goal for the LA Galaxy.
It marked Roldan's third multi-goal game in MLS, and two have come against the Galaxy.
Seattle are top of the Western Conference, equal on points with the Portland Timbers, who recorded a 1-0 win over the Vancouver Whitecaps.
After joining Inter Miami following his Juventus release, Higuain had a tough debut in a 3-0 loss to the Philadelphia Union.
Higuain hit the outside of the post with a bicycle kick and later put a penalty over the crossbar.
Anthony Fontana, Ilsinho and Brenden Aaronson scored for Philadelphia, who are second in the Eastern Conference.
Higuain, meanwhile, has failed to convert his past four penalties in all competitions.
Eastern Conference leaders Columbus Crew fell to a 3-1 loss to Toronto.
The New York Red Bulls thrashed the Montreal Impact 4-1, the New England Revolution beat DC United 2-0 and Chicago Fire overcame Atlanta United 2-0.
Minnesota United played out a goalless draw with Real Salt Lake, while Dallas' clash with Orlando City also finished 0-0.
The San Jose Earthquakes ended a nine-game winless run by beating Los Angeles FC 2-1.
Trailing 4-2 heading into the 90th minute, former Manchester United and Italy forward Giuseppe Rossi reduced the deficit for RSL in Portland – his first MLS goal.
And Sam Johnson completed the stunning comeback against the MLS is Back Tournament champions in the fourth minute of stoppage time.
In a wild showdown, the Timbers opened the scoring through Diego Chara in the sixth minute before RSL's Corey Baird restored parity 13 minutes later, but Jaroslaw Niezgoda's effort within two minutes ensured Portland led 2-1 at half-time.
After Real Salt Lake equalised again, this time courtesy of Damir Kreilach three minutes into the second half, Portland took control of the contest.
Sebastian Blanco's stunning effort with 20 minutes remaining and Felipe Mora's effort five minutes from time seemingly had the Timbers on track before the hosts capitulated.
The Timbers are fourth in the Western Conference, a point above RSL after seven matches.
LA Galaxy beat San Jose Earthquakes for the first time since 2018 thanks to their 3-2 triumph in the California Clasico.
Sebastian Lletget's 82nd-minute goal settled the five-goal thriller after the Earthquakes had led 1-0 and 2-1 against the Galaxy.
After posting just their second win in the regular season, the Galaxy are ninth in the west, while the Earthquakes are eighth.
In other results, Philadelphia Union crushed DC United 4-1, New York City accounted for Chicago Fire 3-1, Dallas defeated Minnesota United by the same scoreline and Orlando City also topped Atlanta United 3-1.
FC Cincinnati played out a 0-0 draw with Columbus Crew, New York Red Bulls drew 1-1 against New England Revolution, while Western Conference leaders Sporting Kansas City were held to a 1-1 draw by Colorado Rapids.
Alan Pulido, Luis Martins and Daniel Salloi all scored within 16 minutes as KC raced to a 3-0 lead. Salloi's classy volley took his tally to nine goals this MLS season.
Israeli midfielder Gadi Kinda added a fourth in the 58th minute with Graham Zusi getting his second assist, before LAFC got a consolation from Danny Musovski.
The win lifted Sporting KC past Seattle Sounders who conceded in the 90th minute to draw 1-1 at home with Dallas.
Fredy Montero had put the Sounders ahead in the 72nd minute with a set-piece header but Dallas equalised from Franco Jara's 90th-minute close-range strike.
Sporting KC are ahead of Seattle on goal difference, with both sides having 33 points, although the leaders have a game in hand.
LA Galaxy are third following a 1-0 victory over Real Salt Lake, secured by Efrain Alvarez's cool 53rd-minute winner.
Eastern Conference leaders New England extended their unbeaten run to five games with a 0-0 draw against Nashville, who slip to fourth despite the result.
The draw also extends Nashville's undefeated streak to nine games.
Former England international Kieran Gibbs netted a 66th-minute equaliser to earn Inter Miami a 1-1 draw away to fellow Florida outfit Orlando City. The goal was Gibbs' first in the MLS.
Philadelphia Union ended their three-game winless run with a 3-0 victory over Toronto after three first-half strikes.
Ola Kamara and Yordy Reyna both netted doubles as DC United won 4-2 over Columbus Crew.
Tomas Pochettino scored a first-half brace as struggling Austin won 3-2 over Houston Dynamo.
Chicago Fire and 10-man New York City played out a goalless draw, while New York Red Bulls and Cincinnati also ended 0-0 and Portland Timbers drew 1-1 with San Jose Earthquakes.
Super sub Ruidiaz came off the bench and scored a delightful game-winning goal just past the hour-mark as the Sounders downed Dallas 1-0 in MLS on Wednesday.
The Sounders were winless in 10 consecutive visits to Dallas (D3 L7, including play-offs) dating back to 2014 – their second-longest winless away run against a single opponent in MLS (11 straight at LA Galaxy from 2010 to 2015).
But Seattle snapped that skid thanks to Ruidiaz as Sporting KC's 1-1 draw with Portland Timbers allowed the Sounders to move top of the west by one point.
Atlanta extended their winning streak to three matches after Ezequiel Barco's first-half goal secured a 1-0 win at home to Toronto.
Since the sacking of head coach Gabriel Heinze following a falling out with star Josef Martinez, Atlanta – who had won successive matches for the first time since the opening two games of the 2020 season entering the fixture – have steadily climbed the table.
Atlanta are three points outside of the play-off positions in the Eastern Conference, which is topped by New England Revolution – 3-2 victors against DC United despite ending the contest with 10 men.
Elsewhere, Rodolfo Pizarro's stoppage-time winner guided Inter Miami to a dramatic 3-2 win against Chicago Fire midweek.
Pizarro struck in the 93rd minute to clinch a third straight home triumph for David Beckham's Inter Miami, who have now lost just once in their last six games.
Philadelphia Union and New York Red Bulls were 1-0 winners over New York City and Columbus Crew respectively, Vancouver Whitecaps topped Austin 2-1, Real Salt Lake defeated Houston Dynamo by the same scoreline, 10-man Montreal drew 0-0 with Cincinnati, while Nashville and Orlando City played out a 1-1 draw.
Roldan struck in the 18th minute for the unbeaten Sounders, who left PayPal Park in San Jose with maximum points on Wednesday.
After the Earthquakes failed to clear their lines, Roldan riffled a thunderous half-volley into the back of the net from outside the penalty area.
The Sounders are now four points clear of the Earthquakes and LA Galaxy, who have played a match less in the west.
David Beckham's Inter Miami – coached by former Manchester United defender and midfielder Phil Neville – suffered a 2-0 defeat at home to Montreal following a 140-minute weather delay.
Bjorn Johnson scored twice in the space of 11 first-half minutes to give visitors Montreal a 2-0 lead inside the opening half an hour in Miami.
The match was then suspended in the 47th minute due to lightning strikes at DRV PNK Stadium, where Montreal held on for victory after more than two hours of waiting.
Montreal top the Eastern Conference, level on eight points with New England Revolution, who played out a 1-1 draw against Philadelphia Union, while Inter Miami have five points from five games.
Elsewhere, Toronto celebrated their first win of the season after topping defending champions Columbus Crew 2-0, Houston Dynamo were 1-0 victors over Sporting Kansas City, while Minnesota United defeated Vancouver Whitecaps by the same scoreline.
The Sounders remain undefeated through six matches this season thanks to a two-goal second half at Lumen Field in Seattle.
Entering the contest, Seattle had 13 points from their first five matches for the second time in the last three seasons – the only team in the last 20 seasons to have at least 13 points after five games more than once.
The Sounders stayed hot courtesy of Xavier Arreaga and Brad Smith – the former opening the scoring in the 57th minute.
Smith doubled the lead with 17 minutes remaining when the Australian full-back pounced for his third goal of the season.
The Sounders are four points clear of LA Galaxy in the Western Conference, while Sporting Kansas City are a point further back in third following their 3-0 win over Vancouver Whitecaps.
LAFC are bottom of the west with five points from five matches in 2021.
Former Juventus and Real Madrid forward Higuain was the hero for Inter Miami, who prevailed 3-2 in a thriller at Cincinnati.
Higuain scored the winning goal five minutes from the end after Cincinnati's Nick Hagglund has restored parity three minutes earlier.
David Beckham's Inter Miami – led by former Manchester United team-mate and head coach Phil Neville – raced out to a 2-0 half-time lead via Brek Shea and Higuain before Cincinnati rallied with goals from Alvaro Barreal and Hagglund.
Former Argentina international Higuain, though, had the final say with his fourth goal of the season.
Elsewhere, New England Revolution topped defending champions Columbus Crew 1-0 and Orlando City beat DC United by the same scoreline.
Orlando have opened the season unbeaten in their first five games (W2 D3). The Lions have lost just three regular-season matches since the end of the MLS is Back Tournament, fewer than any other team that was in MLS both last season and this.
Johnny Russell's 79th-minute goal gave Sporting KC a 2-1 win away to Seattle Sounders, locking up a play-off spot for the second-placed team in the Western Conference table as Russell netted for the seventh straight game.
Colorado also are in after defeating Portland Timbers 2-0 behind golas from Dominique Badji and Diego Rubio.
The Seattle loss ensured New England, who face Orlando City on Sunday, will finish atop the overall table. The Revs are on 69 points, 20 points clear of Philadelphia and Nashville in the Eastern Conference and 11 clear of Seattle overall.
Nashville had a chance to clinch the play-offs with a win but fell 1-0 to Philadelphia Union on Kacper Przybylko's first-half penalty.
Inter Miami got a goal and three assists from Gonzalo Higuain, while his brother Federico also found the net in a 5-1 rout of Cincinnati, who lost their ninth in a row.
Toronto dealt a blow to rival Montreal's play-off hopes as Jozy Altidore's free kick in the fifth minute of stoppage time secured a 1-1 draw after Sunusi Ibrahim had netted in the 55th minute for the visitors.
Minnesota and LAFC also finished at 1-1, as did San Jose Earthquakes and Vancouver Whitecaps.
New York City crushed DC United 6-0 and Sean Nealis' 87th-minute goal lifted New York Red Bulls past Columbus Crew 2-1.
Sebastian Lletget's brilliant 83rd-minute equaliser gave LA Galaxy a 2-2 draw with Dallas, while Chicago Fire downed Real Salt Lake 1-0.
The victory brought the visitors within two points of the first-placed Sounders in the MLS Western Conference table, with one fewer match played.
KC captain Johnny Russell set the tone in the 31st minute with a beautiful free kick from just outside the area to give the visitors the lead, and Daniel Salloi doubled the advantage before half-time.
After Fredy Montero answered for Sounders in the 51st minute, Cameron Duke sneaked behind the defence in the 72nd minute to seal the win.
KC are unbeaten in their last five matches and have only one loss in their last 10.
A brace from Gustavo Bou helped New England Revolution expand their lead atop the Eastern Conference with a 2-1 win over Montreal.
Kacper Przybylko found the net for the third straight game, putting home a rebound in the 85th minute to salvage a 1-1 draw for Philadelphia against Inter Miami as Phil Neville's side remain bottom of the table.
New York City FC matched their season-high in goals, scoring four times after the break in a 5-0 demolition of Orlando City.
Ola Kamara's 27th-minute goal gave DC United a 1-0 victory over New York Red Bulls.
Supporters' Shield winners the Revolution trailed 2-0 with nine minutes of regulation remaining before Poland international Buksa rescued an unlikely point for the high-flying outfit on Sunday.
Buksa pulled a goal back in the 81st minute and then struck in the third minute of stoppage time to salvage a dramatic draw and extend the Revs' undefeated run to nine matches.
Orlando had been in control thanks to quick-fire goals from former Manchester United star Nani and Daryl Pike, who made it 2-0 five minutes into the second half.
With the point, New England (70 through 32 games) – having equalled the record for most road wins in a single regular season in the post-shoot-out era in MLS thanks to Wednesday's 10th away victory – closed within two points of the league record of 72, set by Los Angeles FC in 2019.
Elsewhere, lowly Austin upstaged Houston Dynamo 2-1 courtesy of a two-goal first half.
After Marco Maric's seventh-minute own goal, Sebastian Driussi put Austin 2-0 ahead in the fourth minute of added time in the opening half.
Another own goal, this time in favour of the Dynamo after Julio Cascante's moment of misfortune, made things interesting in stoppage time.
Last season was the first time in Houston's 15 MLS campaigns they finished averaging less than one point per match (0.91 – 21 points in 23 games). With 30 points in 32 rounds this term, the Dynamo are on pace to do so for a second consecutive year.
DC United appeared on track for victory following Nigel Robertha's ninth-minute opener away to New York City on Sunday.
That was until New York City – who have never lost a home match to DC United (W5 D2) – rallied, with Keaton Parks equalising in the 84th minute after flicking home a header from Maxi Moralez's corner.
Thiago then took centre stage in the 95th minute – the Brazilian embarking on a spectacular solo run from his own half, breezing by his opponents and finishing decisively.
New York City have scored in 21 consecutive MLS games (including playoffs). It is the longest active run in the league and longest in club history.
With the win, New York City are fourth in the Eastern Conference – six points adrift of leaders New England Revolution, who lost 2-1 to Dallas.
The Revolution were unable to restore their five-point lead atop the table following Ricardo Pepi's brace for Dallas.
Homegrown star Pepi was the hero for Dallas, who snapped their six-game winless streak by topping the Eastern Conference leaders.
In other results, Atlanta United and New York Red Bulls played out a goalless draw, while Austin and reigning MLS champions Columbus Crew also drew 0-0.
