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.
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.
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.
Australian full-back Brad Smith provided an assist for Ruidiaz's 20th-minute opener, before scoring a goal himself three minutes later, forcing home a rebound.
Ruidiaz settled the contest in second-half stoppage time when he fired home on his left foot from substitute Jimmy Medranda's low cross.
The Sounders dulled the threat of Galaxy forward Javier 'Chicharito' Hernandez – who had scored five goals in his opening two games – in a strong display, where they marginally lost possession but had nine to two shots on target.
The win moves Seattle to seven points from three games to start the new campaign, while the Galaxy suffered their first blemish of the campaign after scoring six goals in their opening two games.
Inter Miami drew a blank in the absence of the Higuain brothers with a 0-0 draw away to Nashville.
Former Juventus and Real Madrid forward Gonzalo Higuain and brother Federico were unavailable for the match after flying back to their native Argentina following the death of their mother to cancer.
The Higuain brothers' team-mates offered a wonderful sign of support ahead of the game.
Inter Miami – co-owned by former Manchester United, Madrid and England star David Beckham – have four points from three games, while Nashville are still winless but have drawn all three matches this season.
Diego Rubio's incredible free-kick helped Colorado Rapids to a 1-0 victory away to Vancouver Whitecaps.
Rubio struck in the 26th minute with a curling right-foot shot that found the top corner, going in off the post and crossbar.
The spectacular strike earned the Rapids their first three points of the season, while condemning the Whitecaps to their first defeat.
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.
Cristian Roldan and Will Bruin scored to lift the Sounders to the summit in the west, leapfrogging hosts Sporting KC.
Sporting KC were on a three-game winning streak against Seattle – the longest active winning run against the Sounders as no team had won four in a row versus the franchise since San Jose Earthquakes in 2012-13.
But Seattle ended that skid against Sporting KC – Roldan opened the scoring in the 31st minute at Children's Mercy Park, where the Sounders star got on the end of Brad Smith's cross.
Bruin doubled the lead against the run of play 10 minutes into the second half after heading home at the far post.
Entering the fixture, the Sounders conceded an MLS-low 20 goals this season, with opponents scoring with just 7.2 per cent of their shots, also lowest in the league. Seattle had also outperformed their expected goals against by 8.1 this season (20 conceded, 28.1 expected).
The Sounders were breached by Johnny Russell on the hour mark, but Seattle held on for victory to sit two points clear of Sporting KC in the west.
Elsewhere, Austin – bottom of the Western Conference – stunned fifth-placed LA Galaxy 2-0, while Chicago Fire held second-placed Nashville to a 0-0 draw in the east.
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.
Cristian Roldan, Jimmy Medranda and Joao Paolo scored in a three-goal first half to inspire the Sounders against the Rapids in Seattle.
The Rapids were enjoying their second-best unbeaten run in club history, only behind the 15-game undefeated streak from April 2016 to July 2016.
But Colorado came unstuck away to the Sounders at Lumen Field, where Roldan broke the deadlock in the second minute before Medranda and Paolo's moment of individual brilliance made it 3-0 prior to half-time.
The Sounders are top of the west, two points clear of Sporting Kansas City, who beat Houston Dynamo 4-2 behind Daniel Salloi's magical performance (one goal and an assist) and Johnny Russell's brace.
Entering the contest, Salloi and Russell had been directly involved, either together or individually, in Sporting KC's previous seven goals (Salloi three goals, Russell three goals and two assists). At least one of those two players had scored or assisted on 19 of the 23 goals Kansas City scored since late July.
David Beckham's Inter Miami and their hopes of featuring in the play-offs were dealt a blow following a 1-0 defeat to Portland Timbers.
Jaroslaw Niezgoda struck to extend Portland's unbeaten run to eight matches, including seven wins, and condemn Inter Miami to a fourth consecutive loss.
Inter Miami are eight points adrift of the post-season places in the Eastern Conference with seven fixtures remaining, while the fourth-placed Timbers are seven points clear of Real Salt Lake in the battle for home-field advantage.
Elsewhere, 10-man Philadelphia Union were 3-0 winners over defending champions Columbus Crew, Toronto defeated Chicago Fire 3-1 and New York City drew 0-0 with Nashville, while the El Trafico derby between LA Galaxy and Los Angeles FC ended 1-1.
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.
Sporting KC scored twice in the closing stages to see off the Galaxy in Los Angeles and leapfrog Seattle Sounders atop the west.
The Galaxy were without former Manchester United and Real Madrid star Javier 'Chicharito' Hernandez after he was a late withdrawal prior to kick-off.
Chicharito scored a brace against San Jose Earthquakes last time out to take his total to 10 goals in 10 games this season – only four players have scored more through their first 10 appearances in an MLS campaign, Carlos Vela (Los Angeles FC) in 2019, Chris Wondolowski (Earthquakes) in 2012, Landon Donovan (Galaxy) in 2008 and Roy Lassiter (DC United) in 1999, all with 11 goals.
The Galaxy felt his absence as visiting Sporting KC – who have scored an MLS-high 24 goals in 2021 – won late thanks to Johnny Russell and Khiry Shelton.
Russell broke the deadlock in the 81st minute with a looping header and Shelton made sure of the points in the fifth minute of stoppage time.
Sporting KC and Seattle are level on 26 points, but the former top the Western Conference with more wins, though they have played a game extra.
The Sounders tied the MLS record with 12 unbeaten games to start the season following their 1-1 draw at Colorado Rapids.
Alex Roldan put Seattle ahead four minutes before half-time, but Colorado's Michael Barrios restored parity approaching the hour-mark.
Elsewhere, lowly Dallas and Vancouver Whitecaps played out a 2-2 draw.
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.
David Beckham's Inter Miami and fellow expansion club Nashville SC will enter the league, which will increase to 26 teams.
Seattle Sounders are the defending champions, record-breaking Los Angeles FC will look to go all the way this year after falling short last term, while Arsenal and Barcelona legend Thierry Henry is at the helm of Montreal Impact.
With the season set to kick off, here is a selection of the best Opta facts related to MLS.
- Only one of the last eight teams to debut in MLS have won their inaugural match, dating back to Portland Timbers in 2011 (LAFC 1-0 Seattle in 2018). Orlando City and New York City drew against each other in both teams' inaugural match in 2015, while the other five teams that joined the league in that time lost their opening match.
- Of MLS' last nine new teams, only one have failed to score in their inaugural match in the competition. Montreal lost 2-0 to Vancouver Whitecaps in 2012.
- Of the 14 teams to play their inaugural MLS match on the road, only two have managed to win; including Los Angeles in 2018 (also Chicago Fire in 1998, at Miami Fusion). Two more managed draws while 10 of the 14 teams that started on the road lost their inaugural match.
- The last six MLS expansion clubs scored in their first away match in the league dating back to 2015. Five of the teams scored one goal while Atlanta United scored six against fellow newcomers Minnesota United in 2017.
- The last three reigning MLS Cup winners lost the opening match of the following season, including Seattle's 2-1 defeat at Houston Dynamo in 2017 after reigning supreme in 2016.
- LAFC equalled the all-time record for goals scored in a single MLS season last campaign (85 – level with LA Galaxy in 1998). Their striker Carlos Vela also broke the record for single-season goals in MLS history; scoring 34 and beating Josef Martinez's record haul of 31 from 2018.
- Atlanta star Martinez has scored a goal against all 23 of the opposition teams that he has faced in regular-season MLS matches – Nashville will be the 24th different opponent he has played against in the competition.
- New York City's 177 points and 50 wins are both second-most over the past three MLS regular campaigns, both behind Atlanta (182 points and 54 wins). NYC are the only team that have won at least 16 regular-season matches in each of the past three MLS campaigns.
- Last season was the 10th straight in which New York Red Bulls qualified for the MLS postseason. The Red Bulls' 10 successive play-off appearance represent the second-longest active run (Seattle – 11) and the longest in the history of the Eastern Conference.
- New Impact manager Henry took charge of Monaco in Ligue 1 last season between October 2018 and January 2019. During his 12 league games in charge, he won just twice (17 per cent); which was the worst win ratio of every Monaco head coach to take charge of five-plus top-flight games in their history.
- Colorado Rapids have missed the play-offs in three successive MLS seasons for the first time since 2007-2009. They have collected just 106 points over the past three MLS campaigns, only Orlando City (104) have collected fewer among the teams that have been in the league for each season since 2017.
- 85 of LA Galaxy recruit Javier Hernandez's 89 goals within the big five European leagues during his career came from inside the box (96 per cent), including each of the past 30 of these strikes.
Toronto moved level on points with Philadelphia after a 2-1 win over Inter Miami and the Union's 2-1 defeat to Columbus Crew on Sunday.
Columbus took a 37th-minute lead at home, Artur finding the bottom corner from 20 yards.
However, Philadelphia drew level in the 57th minute thanks to a penalty from Jamiro, although the hosts would strike late.
Krisztian Nemeth got on the end of a Luis Diaz Espinoza cross from the right to tap away a winner six minutes from time for Columbus, who are third in the Eastern Conference.
Toronto boosted their chances of winning the Supporters' Shield by overcoming Inter Miami.
Former Juventus midfielder Blaise Matuidi opened the scoring for Inter Miami with his first MLS goal.
But Toronto would win after conceding the opening goal for the third time this season, which is tied for the most with San Jose Earthquakes, as per Opta.
Ayo Akinola scored a fine equaliser after outmuscling his opponent before Gonzalo Higuain almost responded for Inter Miami, hitting the crossbar with a powerful 20-yard effort in the 79th minute.
Instead, Alejandro Pozuelo tucked away an 84th-minute penalty for the winner for Toronto.
Pozuelo has scored each of his past seven penalties for Toronto in MLS.
Valentin Castellanos scored a hat-trick to inspire New York City to a 5-2 derby win over the Red Bulls.
Castellanos became just the second player to net a hat-trick in the Hudson River Derby, joining David Villa (2017).
Elsewhere, Teal Bunbury's brace saw New England Revolution overcome DC United 4-3 in a thriller and Atlanta United beat Cincinnati 2-0.
Orlando City edged Montreal Impact 1-0, Colorado Rapids beat Seattle Sounders 3-1, the Portland Timbers overcame the Vancouver Whitecaps 1-0 and LA Galaxy edged Real Salt Lake 2-1.
