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.
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.
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.
The Cascadia derby did not disappoint on Sunday, with the Sounders snapping a three-game winless streak behind Montero and Ruidiaz.
Entering the fixture, the slumping Sounders had won three of their last four away matches against the Timbers (L1) after winning just three of the first 14 MLS encounters in Portland (D3 L8, including play-offs).
Montero scored twice inside the opening 29 minutes to put the Sounders in control before Sebastian Blanco and George Fochive restored parity for the Timbers by the 52nd-minute mark at Providence Park.
Beginning with the 2018 playoffs, Ruidiaz had scored (eight) or assisted (two) on 10 of the Sounders' last 14 goals against the Timbers, including seven of eight goals in Portland (five goals and two assists) during that time.
Ruidiaz turned Sunday's match on its head with a stunning brace, including his memorable 55th-minute free-kick.
Jimmy Medranda's thunderous 77th-minute volley and Nicolas Benezet's stoppage-time effort completed the rout.
Seattle are second in the Western Conference, only a point behind Sporting Kansas City after 19 games, while Portland are eighth.
Elsewhere, Josef Martinez celebrated a long-awaited home goal as Atlanta United edged Los Angeles FC 1-0.
Martinez had not scored at Mercedes-Benz Stadium since October 2019, but the Venezuelan star ended his drought in the 47th minute.
Nashville are third in the Eastern Conference following their 5-2 drubbing of DC United – a victory inspired by CJ Sapong's brace, while snapping DC United's five-game unbeaten streak.
Chicago Fire topped defending champions Columbus Crew 1-0 via Luka Stojanovic's winner with 15 minutes remaining.
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.
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.
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.
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.
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.
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.
The Whitecaps took a 12th-minute lead from Tristan Blackmon's instinctive close-range finish, but the 2019 MLS champions rallied, led by former Mexico international Vela.
Vela's 27th-minute corner was met by Hollinghead with a powerful header for the equaliser before the ex-Arsenal attacker struck at the second attempt with a 38th-minute left-foot volley.
Hollingshead wrapped up all three points with the pick of the goals, unleashing a fine low right-foot strike from the edge of the box in the 70th minute.
The result means LAFC have collected 10 points from four games, to sit atop the Western Conference with the best record in the MLS. Winless Vancouver have one point from four games.
Darlington Nagbe poked home a dramatic 95th-minute equaliser as Columbus Crew snatched a 1-1 draw at New York Red Bulls, denying the hosts top spot in the Eastern Conference.
Tom Barlow had inadvertently put the Red Bulls ahead in the 84th minute from a scramble following a corner but Nagbe pinched a point late after reacting quickest from Steven Moreira's low cutback.
Diego Fagundez earned Austin a 1-1 home draw with Seattle Sounders with a 70th-minute strike, after Will Bruin opened the scoring in the 43rd minute from Cristian Roldan's assist.
Seattle's Kelyn Rowe came closest to a winner with a 74th-minute effort hitting the crossbar.
Birthday boy Vela scored a stunning chip on the stroke of half-time to ensure reigning Supporters' Shield champions LAFC made the perfect start to the 2020 season on Sunday.
Co-owner David Beckham, his famous wife Victoria and Inter's hierarchy were in the stands as the expansion franchise made history in Los Angeles.
Inter battled in their first-ever MLS match but Diego Alonso's side came unstuck following a moment of brilliance from Vela on his 31st birthday.
Former Arsenal forward Vela – who scored a record-breaking 34 goals in a MVP season last term – chipped the ball over Inter captain and goalkeeper Luis Robles in the 44th minute at Banc of California Stadium.
"Surely we have to improve in football, but with this heart and with this intensity with which the team plays, we will surely win many games," said Inter head coach Alonso.
"Against maybe the best team in the league we gave a tremendous picture today of what we can become. With only six weeks of work, the merit is certainly from the footballers for what we have done today and the work they have done."
Seattle Sounders started their title defence with a dramatic 2-1 victory at home to Chicago Fire thanks to substitute Jordan Morris' brace.
Trailing to Robert Beric's 46th-minute opener, the Sounders equalised via Morris just past the hour mark before he netted the winner in the third minute of stoppage time.
Elsewhere, Kevin Molino scored twice as Minnesota United upstaged Portland Timbers 3-1, New York Red Bulls edged Cincinnati 3-2 and 10-man New York City lost 1-0 away to Columbus Crew.
The Crew returned to winning ways in style following their defeat to Inter Miami, beating Kansas City 4-0 last time out courtesy of Cucho Hernandez's hat-trick.
Nancy's side sit in fifth place in the Eastern Conference, two points behind Charlotte FC but with the luxury of three games in hand compared to Dean Smith's side.
Despite their convincing victory in their last MLS fixture, Nancy is looking to replicate the Crew's four-game unbeaten run they enjoyed last month moving forwards.
“It was really important also when I made all the changes that we stay focused on the task,” Nancy said.
“With all the celebration also was not easy because we can switch really quickly.
"I really wanted to help my team to have a clean sheet if possible and to score more goals because this is the level that we want to have. I don't like when we take everything for granted.”
Meanwhile, the Revs also come into the fixture on an impressive run of form, beating high-flyers FC Cincinnati 2-1 away from home to extend their winning streak to four matches in the MLS.
Caleb Porter's side welcome the Crew to the Gillette Stadium this weekend in search of improving their home form to climb up the Eastern Conference table.
New England have won just three of their last seven games in front of their supporters and know a win will see them move up from 12th in the standings, along with games in hand on many of the surrounding sides.
PLAYERS TO WATCH:
New England – Cucho Hernandez
Cucho Hernandez scored his third career MLS hat-trick in the Crew’s win over Kansas City on Saturday, with all three coming within his last 20 games.
The Colombian is just the ninth player in MLS history to score three hat-tricks in a span of 20 games.
Columbus Crew – Giacomo Vrioni
It looks set to a battle of both side's goal-scoring forwards, with Giacomo Vrioni looking to continue his hot streak for Nancy's side.
Vrioni scored both of New England’s goals against Cincinnati on Saturday, the first time a Revolution player has scored more than one goal in a game this season.
MATCH PREDICTION: COLUMBUS CREW WIN
The Crew come into the encounter in much the better form, having won five of their last six league matches (L1) following their win over Sporting Kansas City.
However, New England also boast an impressive winning streak of their own. Porter's side have won four consecutive matches, having previously won just four of their previous league matches dating back to the beginning of September last year (D4 L14).
And it was the Crew who emerged victorious in the side's last meeting. The win over New England last October ended a string of five straight draws between the sides. Columbus have lost only one of their last 12 against New England (W5 D6) dating back to 2018.
OPTA WIN PROBABILITY
New England - 27.1%
Draw - 23.9%
Columbus Crew - 49%
Alexander Ring tapped in a 59th-minute winner after a poor error by Columbus at Red Bull Arena.
City moved up to 10th in the Eastern Conference with just their second win in seven MLS games, while Columbus remain top by a point despite their first loss.
Just eight minutes before the opener, City went close through Alexandru Mitrita, whose long-range effort hit the crossbar.
But a terrible mistake by Aboubacar Keita handed New York City the opener – and winner.
Keita's pass across defence was easily intercepted by Heber, who cutback for Ring to tap in the easy winner.
