United made the perfect start when Bruno Fernandes converted a second-minute penalty but found themselves a goal behind when Tanguy Ndombele and Heung-Min Son turned the game around inside a frantic first seven minutes.
Anthony Martial was shown a straight red card for lashing out at Erik Lamela on 28 minutes, and Spurs added salt to United wounds as Harry Kane’s first and Son’s second saw the hosts concede four goals in the first half of a Premier League for the first time.
Serge Aurier rifled Spurs’ fifth early in the second and Kane added a sixth from the penalty spot 10 minutes from time as Jose Mourinho haunted his former club on his second return to Old Trafford.
Spurs climb to fifth in the Premier League – two points behind fourth-place Arsenal – after securing their second win of the campaign, while United drop to an unfamiliar 16th after a performance Sky Sports’ Gary Neville labelled “pathetic, absolutely pathetic.”
Man Utd: De Gea (4), Wan-Bissaka (4), Bailly (2), Maguire (2), Shaw (3), Matic (4), Pogba (3), Greenwood (5), Fernandes (5), Rashford (4), Martial (3).
Subs: Fred (4), McTominay (4), Van de Beek (5).
Tottenham: Lloris (7), Aurier (9), Sanchez (7), Dier (7), Reguilon (8), Hojbjerg (8), Sissoko (8), Ndombele (8), Lamela (7), Son (9), Kane (9).
Subs: Davies (7), Alli (7), Moura (6).
Man of the Match: Harry Kane.