The first chance fell unsurprisingly fell to Romelu Lukaku, but the Belgian blasted wide of the post after 10 minutes.
All the while, Brighton showed plenty of enthusiasm with their forward play but lacked the necessary skills to penetrate United’s defence.
The Seagulls raced into the lead after a cross from Solly March picked out Glenn Murray to flick home at the near post on 27 minutes.
Shane Duffy then doubled Brighton's lead two minutes later with a low strike in the box, before United reduced the deficit as Lukaku nodded home from close range.
A poor challenge from Eric Bailly inside the box led to a spot kick and Pacal Gross took full advantage with a cool 12-yard finish for a healthy lead at the break.
The Red Devils made a double switch at the start of the second half, with Marcus Rashford and Jesse Lingard replacing Andreas Pereira and Juan Mata respectively.
Following a quieter start to the second period, United introduced their final change as Marouane Fellaini replaced Anthony Martial on 60 minutes.
A bit of brilliance in goal from Matt Ryan prevented Paul Pogba in his tracks from getting his second of the season with a shot from range, allowing the Albion’s defence to clear away.
United were handed a penalty after a foul on Maroune Fellaini inside the box, Pogba converted to reduce the score-line slight but Brighton held firm for yet another famous win over United.