First-half goals from Glenn Murray, Shane Duffy and Pascal Gross gave the hosts a third league win in a row against the Red Devils on home soil, a run that stretches back to 1982.
Romelu Lukaku got on the scoresheet for the first time this season, while Paul Pogba converted an injury-time penalty, but the victory was no more than Brighton deserved, with Jose Mourinho's side poor throughout.
Brighton took control in the first half-hour thanks to two goals in the space of 143 seconds, with Murray clipping a delightful finish past David de Gea before Duffy swept home after United failed to clear a corner.
Lukaku, who missed a golden chance at 0-0, nodded in a lifeline for his side but more slack defending saw Eric Bailly bring down Gross, who dispatched his penalty a minute before the break.
With Alexis Sanchez missing the game through injury, Mourinho introduced Marcus Rashford and Jesse Lingard at half-time, but there was little improvement to their attacking display and Pogba's finish from the spot came too late to rescue a result.
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United's defending was dire, with Bailly and Victor Lindelof doing little to convince the manager of their suitability as a long-term partnership, while Andreas Pereira and new recruit Fred were anonymous in midfield.
Disjointed as United looked, Brighton appear to be going from strength to strength under Hughton. This was an improvement on their display in last season's 1-0 home win over the same opponents and will give the manager hope of a top-half finish this term.
The Red Devils must get better, though, and quickly, or the title will start to look beyond their reach even before the race has truly begun.
10 - This is only the tenth time in Premier League history that Manchester United have conceded three first half goals in a game, and the first time since October 2015 v Arsenal. Porous.— OptaJoe (@OptaJoe) August 19, 2018
Pat on the back: Murray magic for Brighton
Murray is 35 next month, but you would be forgiven for thinking he is 10 years younger given his display here.
His goal was a quite superb first-time finish and he generally ran Bailly and Lindelof ragged, allowing the home side plenty of reprieve from any United pressure during the second half.
Boot up the backside: Bailly abysmal
Not long after signing two years ago, Bailly looked every bit a top-class United centre-back in the making. After this performance, he could face a battle to stay in his manager's plans.
His positioning was generally poor, he conceded a needless corner from which Brighton scored their second, while his rash challenge on Gross gifted them the third from the penalty spot.
Key Opta Facts
10 - In competitive games since the start of the 2018 World Cup, David de Gea has conceded 10 goals from his last 14 shots on target faced for Manchester United and Spain combined. Glum. pic.twitter.com/Hk2T64n916— OptaJoe (@OptaJoe) August 19, 2018
- Since taking charge of Manchester United at the start of the 2016/17 season, the only opponent Jose Mourinho has lost against more often than Brighton (2) is his former club Chelsea (4).
- United lost their first away game of a Premier League campaign for the first time since 2012/13, when they went down 1-0 to Everton at Goodison Park.
- Pascal Gross has scored eight goals in the Premier League, all at home. Only two players have netted more goals exclusively at home in the competition’s history – Georginio Wijnaldum (18) and Clive Wilson (9).
- Paul Pogba ended on the losing side in a Premier League game he scored in for the first time – United had won each of the previous 11 games he had netted in, a joint-record in the competition (with Ryan Babel for Liverpool – 11 games).
- This was only the 10th time in Premier League history that Manchester United conceded three first-half goals in a game, and the first time since October 2015, against Arsenal.
Brighton face another sizeable challenge in the form of Liverpool at Anfield next Saturday, where they lost 4-0 on the final day of last season. Indeed, they have not won away from home in the top flight since last November.
United will host Tottenham next Monday, with Mauricio Pochettino's side likely to have been encouraged by the performance of Mourinho's men on the south coast.