The Black Cats took the lead in the third minute when De Gea was duped by a long-range free kick from Wahbi Khazri, with Jermain Defoe’s late attempt to backheel the ball past the keeper potentially distracting the Spain international at the last minute.
Anthony Martial equalised before halftime with a chip over Vito Mannone, but De Gea was guilty late on when his error handed Sunderland a late lead as he fumbled Lamine Kone’s header over the line.
Sam Allardyce’s men began the day in 19th place, mired in a relegation battle, but the win will lift them level on points with 19th-place Norwich City, who are on a five-game losing streak and face West Ham United later this weekend.
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The loss also jeopardises United’s hopes of securing a spot in next year’s Champions League, with the Red Devils failing to close the gap to the teams ahead of them.
If Manchester City defeat Tottenham Hotspur on Sunday, the Red Devils will fall a whopping nine points behind their city rivals.