The Galaxy, who were without Javier Hernandez due to injury and Jonathan dos Santos, Efrain Alvarez and Sebastian Lletget to Gold Cup call-ups, were brushed aside by Dallas who were last in the Western Conference prior to the game.
Pepi, who turned 18 in January, becomes the youngest player in MLS history to net a hat-trick.
The teenager netted twice in the first half before completed his treble with a low shot from the edge of the box in the 50th minute.
Substitute Jader Obrian added another in the 88th minute as Dallas moved up to 10th in the west, while the Galaxy are third but are winless in their past three.
Carlos Vela got on the scoresheet as LAFC came from two goals down to rescue a 2-2 home draw with struggling Vancouver Whitecaps.
Colombian pair Deiber Caicedo and Cristian Dajome had put the Whitecaps two-up inside the first 38 minutes, before Vela pulled one back in the 40th minute.
Diego Palacios provided the pass for fellow Ecuadorian Jose Cifuentes to level in the 75th minute.
Charles Sapong scored twice as Nashville SC moved up into second spot in the Eastern Conference with a 3-0 victory over Cincinnati.
Toronto maintained their good recent run with a 2-1 win at Chicago Fire, while Minnesota United scored twice in the final 20 minutes to win 2-1 over Portland Timbers.
San Jose Earthquakes drew 1-1 with Houston Dynamo and Real Salt Lake won 3-0 over Colorado Rapids.
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.
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.
Sergio Santos netted three times as Philadelphia crushed Toronto 5-0 at Subaru Park on Saturday.
The result equalled the Union's biggest ever win and Toronto's largest defeat, as per Opta.
Philadelphia needed until the 27th minute to get going, Sergio Santos heading in a wonderful cross from Kai Wagner.
Just six minutes later and the hosts doubled their lead, Mark McKenzie heading in from close range after a corner.
Jamiro scored a spectacular third for Eastern Conference leaders Philadelphia in the 56th minute, his 20-yard effort going in off the underside of the crossbar.
Sergio Santos put away two more to complete his hat-trick – the fourth in the Union's history and first since C.J. Sapong in May 2017.
Western Conference leaders Sporting also enjoyed a fine win, thrashing the Colorado Rapids 4-0.
Alan Pulido, Andreu Fontas, Gadi Kinda and Gerso Fernandes netted in the victory.
Leandro Gonzalez Pirez's 89th-minute winner saw Inter Miami – without the suspended Gonzalo Higuain – edge Orlando City 2-1, while DC United overcame Atlanta United 2-1.
New York City recorded a 3-1 victory over the Montreal Impact and the Vancouver Whitecaps were too good for the San Jose Earthquakes 2-1.
The Chicago Fire and New York Red Bulls drew 2-2, Minnesota United edged Cincinnati 1-0, Houston Dynamo and Columbus Crew drew 1-1 and Real Salt Lake and Dallas played out a goalless draw.
After Raul Ruidiaz's 40th minute opener, the visitors had taken the lead after goals from Cristian Dajome and Lucas Cavallini.
Medranda intervened with his 71st minute strike, coming after a corner was cleared into his path, lashing home from the edge of the box.
The result means Seattle remain top in the Western Conference, having conceded only seven goals in 11 games.
It also ends Vancouver's five-game losing streak, although they remain second last in the west.
Former Manchester United striker Javier 'Chicharito' Hernandez scored a double to lift LA Galaxy to a 3-1 win away to San Jose Earthquakes.
The Mexico international opened the scoring in the 11th minute when he swept home Samuel Grandsir's dangerous cross from the right.
Hernandez produced a similar finish to double their advantage in the 50th minute, tapping home from Kevin Cabral's ball.
Galaxy are third in the Western Conference, four points behind Seattle with a game in hand.
Philadelphia Union extended their unbeaten run to eight games with a 3-3 draw away to Chicago Fire.
Toronto's struggles continued with a 2-0 home defeat to Cincinnati, condemning them to five consecutive defeats.
Sporting Kansas City defeated Los Angeles FC 2-1, Real Salt Lake and Houston Dynamo drew 1-1, Minnesota United won 1-0 at Portland Timbers and Abu Danladi netted a late leveller to help Nashville claim a 1-1 home draw with Montreal.
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.
Ruidiaz scored twice in the second half after Joao Paulo's memorable opener to give last season's runners-up Seattle the perfect start on opening day.
The Sounders – beaten by Columbus Crew in the 2020 MLS Cup final – hit the front four minutes into the second half, Joao Paulo cushioning a cleared cross with one touch before rifling a thunderous volley into the top corner on Friday.
Ruidiaz entered the new season on the back of 12 MLS goals last term. According to Stats Perform, his 0.76 goals per 90 minutes led the league in 2020. When the Peruvian star was on the field, the Sounders scored two goals per 90 – besting their average of 1.5 goals per 90 when he was not last year.
A dominant force in the Western Conference since Brian Schmetzer succeeded legendary former boss Sigi Schmid in 2016, the Sounders doubled the lead with 20 minutes remaining when Will Bruin teed up Ruidiaz.
Ruidiaz made it 3-0 three minutes later after Cristian Roldan turned provider before Fredy Montero completed the rout four minutes from time at CenturyLink Field in Seattle, where the Sounders had an expected goals (xG) difference of 20.9 last season, well clear of next-best team Los Angeles FC (12.0)
In the only other match on Friday, Houston Dynamo edged San Jose Earthquakes 2-1.
Houston built a two-goal buffer by the 55th minute thanks to Memo Rodriguez and Maximiliano Urruti.
A stunning 74th-minute strike from San Jose substitute Paul Marie set up a tense finish, but the Dynamo held on for maximum points.
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.
Johnny Russell scored a goal and assisted two others as Sporting KC routed Minnesota at Children's Mercy Park on Wednesday.
Russell converted a penalty as part of a three-goal first half, with Khiry Shelton and Daniel Salloi also on target against the visitors.
Cameron Duke added a fourth goal seven minutes into the second half as Sporting KC found the back of the net in their 28th consecutive regular-season home game dating back to August 2019 – the longest active streak in MLS.
Sporting KC are a point clear in the west, though second-placed Seattle Sounders have played two games less, while Minnesota are two points outside the play-off positions.
San Jose Earthquakes star Javier Lopez scored a hat-trick, but Real Salt Lake still prevailed 4-3 in a wild clash.
Lopez opened the scoring in the 26th minute and completed his treble in the second half, however, RSL emerged victorious thanks to Rubio Rubin's brace.
The result snapped a five-match away losing streak for RSL, who ended San Jose's run of three consecutive wins over their rivals in MLS – a run that had equalled the longest streak by either team in history.
Elsewhere, former Manchester United and Real Madrid striker Javier 'Chicharito' Hernandez salvaged a 1-1 draw for LA Galaxy against Houston Dynamo.
Another ex-United star, Nani, was sent off in the first half as Orlando City were beaten 4-2 by Montreal, Ola Kamara's opening-half hat-trick lifted DC United past Chicago Fire 3-0, Atlanta United were 4-0 winners against FC Cincinnati courtesy of a Josef Martinez double, Los Angeles FC edged Austin 2-1 and 10-man Portland Timbers drew 2-2 with Colorado Rapids.
Sibling pair Diego and Yimmi Chara were among the goals as the Timbers – unbeaten in six matches – eased past RSL at Providence Park on Saturday.
Felipe Mora, Dairon Asprilla, Jaroslaw Niezgoda and Cristhian Paredes also scored for the Timbers, who have netted in 16 consecutive matches against RSL (including play-offs) – the second longest streak against any opponent in their history, behind the 17 straight versus Dallas from August 2012 to March 2018.
The Timbers led 2-1 at half-time before putting RSL to the sword in the second period to match their six-game unbeaten streak from September-October last season.
Portland are fourth in the Western Conference, six points behind leaders Sporting Kansas City, while RSL occupy the seventh and final play-off position in the west.
Los Angeles FC are three points outside the top seven following their 2-0 defeat to San Jose Earthquakes, while Vancouver Whitecaps are also on 33 points after topping Dallas 1-0.
The Union defeated Atlanta 1-0 thanks to Kacper Przybylko's goal with less than 20 minutes remaining.
Back-to-back wins sent Philadelphia up to fourth in the Eastern Conference as Atlanta's three-game winning streak came to an end to leave them eighth in the east and outside the post-season positions.
In other results, Supporters' Shield leaders New England Revolution were 2-1 winners over Orlando City.
The Revolution extended their MLS single-season record for wins by one-goal margins to 16. Nine of New England's last 10 MLS victories have come by a one-goal margin.
It continued Orlando's misery against New England – the team have never won at the Revolution (D1 L5), the only side they have visited more than three times without recording a victory in MLS play.
DC United prevailed 4-2 against FC Cincinnati, New York Red Bulls overcame rivals New York City 1-0, defending champions Columbus Crew won 2-1 against Montreal, Houston Dynamo lost 2-0 to Minnesota United, while Colorado Rapids and Toronto played out a 0-0 draw.
Patrick Mullins' first-half goal saw Toronto edge FC Cincinnati 1-0 on Sunday to book a spot in the play-offs.
Mullins produced a side-footed finish from inside the area after a Richie Laryea cutback just before the half-hour mark.
Toronto are top of the Eastern Conference and three points clear of Philadelphia Union.
Philadelphia won six straight home regular-season matches for the first time in their history, as per Opta, thanks to a 2-1 win over Montreal Impact.
Danny Musovski scored a double as LAFC enjoyed a 3-1 victory against Seattle Sounders.
LAFC are fourth in the Western Conference, which the Sounders top.
Erik Hurtado scored a spectacular volley to see Sporting Kansas City edge a 10-man Nashville 2-1.
Hurtado produced a wonderful finish from Amadou Dia's lofted pass to earn Sporting three points.
New England Revolution beat New York City 2-1, Chicago Fire were 2-1 winners over DC United and Jaroslaw Niezgoda netted twice as Portland Timbers claimed a 3-0 victory against San Jose Earthquakes.
Alejandro Pozuelo's fine run of form continued as Toronto came from behind to beat the Philadelphia Union 2-1 in Connecticut.
Sergio Santos' delicate chip had put Philadelphia ahead in the fifth minute, but Toronto fought back in the second half.
Ayo Akinola headed in a Tony Gallacher cross from the left approaching the hour-mark to bring Greg Vanney's side level.
Pozuelo scored what proved to be the winner in the 76th minute, heading in at the back post following a corner.
As Toronto won for the 10th time in their past 13 meetings with the Union, Pozuelo has been directly involved in 10 goals since the MLS regular season resumed in August, as per Opta.
Toronto joined Columbus on 31 points atop the Eastern Conference after the Crew were held to a 2-2 draw by Dallas.
LA Galaxy are bottom of the Western Conference after slumping to a 2-1 loss to the San Jose Earthquakes in the California Clasico.
The Galaxy seemed on track when Sebastian Lletget put away the opener after Javier Hernandez hit the post, and goalkeeper David Bingham saved Chris Wondolowski's 12th-minute penalty.
But Marcos Lopez drilled in a wonderful equaliser before half-time, and Andres Rios made no mistake with San Jose's second spot-kick of the game in the 82nd minute.
Orlando City continued their fine season with a 3-1 victory over the New York Red Bulls.
The club's tally of 29 points from their first 15 matches is five more than they have ever had through the same number of games in any previous campaign, according to Opta.
Gonzalo Higuain's Inter Miami fell to a 3-2 loss to New York City, while Atlanta United crushed DC United 4-0.
Montreal Impact and Chicago Fire drew 2-2, Alan Pulido scored a brace as Sporting Kansas City edged Houston Dynamo 2-1 and Minnesota United enjoyed a 2-0 victory over Cincinnati.
Western Conference leaders the Seattle Sounders beat the Vancouver Whitecaps 3-1, while the clash between the New England Revolution and Nashville finished goalless.
