Woeful defending led to two Brighton goals in two first-half minutes as 34-year-old Glenn Murray and Shane Duffy outsmarted United's 117 million pound ($149.21 million) back four to demonstrate why manager Jose Mourinho had sought to upgrade it.
Striker Glenn Murray scored a brace and Jose Izquierdo curled in a shot from outside the box to lift promoted Brighton to 10th in the standings, leaving West Ham in 17th just above the relegation zone.
Wayne Rooney ended his eight-game Premier League scoring drought with a 2-0 victory against a dogged Sunderland.
Crystal Palace left Manchester City's hopes of retaining their Premier League crown in tatters after a 2-1 win at Selhurst Park on Monday to leave Manuel Pellegrini's side trailing a distant fourth in the title race.
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The visitors went ahead through Eric Maxim Choupo-Moting but Pascal Gross equalised just before the break only for Kurt Zouma to head Stoke back in front moments later. Jose Izquierdo then levelled for Brighton on the hour to earn a deserved point.
Runaway Premier League leaders Manchester City beat champions Chelsea 1-0 at the Etihad Stadium on Sunday to extend their lead to 18 points and leave the London side further adrift from the Champions League qualification spots.
Harry Kane became Tottenham's joint fifth highest scorer as he helped his side earn a 2-1 Premier League victory over Brighton & Hove Albion on Saturday.
Liverpool beat Leicester City 2-1 to post a fourth successive Premier League victory but conceded their first goal of the season after a nightmare mistake by new keeper Alisson.
Cardiff had lost six of their previous seven games but, knowing that anything but a victory would probably end their survival hopes after one season in the top flight, overcame a strong Brighton start to play with growing confidence and fully deserved their victory.
Pep Guardiola's insatiable team were already thinking beyond the magnificent 2018-19 campaign and contemplating a third straight English title win next season with the Spaniard having said they will get even better.
After bagging the League Cup, being locked in a titanic battle with Liverpool for the Premier League title and in the Champions League quarter-finals, Pep Guardiola's side remain on course for an unprecedented clean sweep.
Liverpool cranked up the pressure on West Ham United manager Slaven Bilic with a 4-1 victory at the London Stadium, while Burnley's remarkable start to the Premier League season continued thanks to a 1-0 victory at Southampton on Saturday.
Brighton and Hove Albion made sure of Premier League football next season with two games to spare after a Pascal Gross goal gave them a memorable 1-0 home win over Manchester United on Friday.
Manchester City soared above the fog swirling round the Etihad Stadium to demolish Tottenham Hotspur 4-1 and leave the rest of the Premier League peering into the distance in search of Pep Guardiola's record-breaking team on Saturday.
Images from the EPL matches played on Sunday
Aston Villa were crushed 6-1 by Southampton but joined Leicester City in celebrating Premier League survival on Saturday while Steven Gerrard's farewell party was spoiled as Liverpool lost 3-1 to Crystal Palace.
The win moved Spurs up to third but unbeaten Manchester City still looked in a class of their own at the top as Leroy Sane scored twice in a 4-0 stroll over West Ham United.
Manchester United climbed back up to second in the table after second-half goals by Anthony Martial and Jesse Lingard earned a 2-0 victory at Everton -- their first win in five games in all competitions.
Images from the English Premier League matches played on Saturday
Manchester City claimed the win required to finally end Liverpool's relentless attempt to dethrone them as Premier League champions as they hit back from a goal down to crush Brighton and Hove Albion on the south coast on Sunday.
Sergio Aguero scored five times in 20 minutes including an eight-minute hat-trick as Manchester City came from behind to thrash Newcastle United 6-1 and go back to the top of the Premier League table on Saturday.
IMAGES from the English Premier League matches played on Saturday.
Liverpool's Egyptian forward Mohamed Salah scored his 29th Premier League goal six minutes from time to secure a 2-1 win at Crystal Palace that took them up to provisional second spot in the table on Saturday.
The following is a look back on key moments in the thrilling Premier League title race, won by Manchester City on Sunday:
Images from the English Premier League matches played on Tuesday
Arsenal's victory was scrappy and nervy but Laurent Koscielny's 72nd-minute winner was enough to move them two points clear at the summit after LeicesterCity's surprise push faltered with a goalless draw at home to 10-man Bournemouth.
Images from the English Premier League matches played on Saturday
A preview of the line-up action in the English Premier League from October 20-22.
Match-by-match facts and statistics ahead of the Premier League fixtures on April 28-30
A summary of Saturday's matches in the English Premier League.
News of all that's transpired on and off the football field
Images from the EPL matches played on Saturday
The 78th Annual Golden Globe awards have been announced. A quick look at the winners.
Following is a match by match look at the English Premier League's weekend fixtures:
Images from the English Premier League matches played on Saturday.
A quick look at the winners of the 93rd Annual Academy Awards, listed in bold.
IMAGES from Saturday's English Premier League matches.
Two big derbies and an eventful weekend of football awaits us all...