Crystal Palace have a first league win at Old Trafford since 1989 and Manchester United have questions to answer.
In a frantic finish an 88th-minute Daniel James curler seemed to have grabbed United a point yet as added time arrived Paul Pogba squandered possession and Palace moved upfield before Patrick van Aanholt beat David de Gea from close range.
Marcus Rashford had earlier taken over penalty duties following Pogba’s miss at Wolves on Monday yet the No 10 could only cannon the ball off Vicente Guaita’s right post, missing the chance to equalise Jordan Ayew’s first-half opener.
That had been Palace’s first goal of the season and Van Aanholt secured their first points.