Diogo Dalot and Rasmus Hojlund scored second-half goals to give Erik Ten Hag's side the three points, but Newcastle's victory at Brentford means the Red Devils finish in eight place, their lowest league finish since 1989/90, and miss out of European qualification from their league standing.
Brighton dominated for large periods of the game in Roberto De Zerbi's farewell fixture, and should have found themselves ahead at the break on a sunny day at the Amex Stadium.
Rasmus Hojlund soon doubled United's lead. He combined with fellow substitute Christian Eriksen, before driving the ball low into the net with his weaker right foot.
Erik ten Hag's men travel to Wembley next week, where they face Manchester City, fresh from wrapping up their unprecedented fourth Premier League title in a row.
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