Brighton survived a late onslaught to secure a first win at Old Trafford and condemn Erik ten Hag to a losing start as Manchester United manager.
Pascal Gross' first-half double stunned the home supporters, who were desperate to see their team put a miserable end to last season behind them.
However, United were totally outplayed in that opening period by Graham Potter's team, who beat them 4-0 at the Amex Stadium in May on their way to a ninth-placed finish, their highest in the top flight.
Not even the second-half introduction of Cristiano Ronaldo could deny Brighton, although they did threaten a comeback when a scramble inside the visitors box ended with Alexis Mac Allister turning the ball into his own net after goalkeeper Robert Sanchez had touched it into his path under pressure from Harry Maguire.