Bruno Fernandes missed a 93rd-minute penalty as Aston Villa won 1-0 at Old Trafford Saturday.
Kortney Hause had put Villa ahead with a powerful header two minutes from the end of normal time before the defender handled inside the box to present United with a lifeline.
However, Fernandes blazed over high over the bar in front of the Stretford End as United’s unbeaten start to the Premier League season came to an end.
Having suffered an early Carabao Cup exit at home to West Ham, United have lost their past two games without scoring.
Elsewhere, Gabriel Jesus’ deflected effort was enough to give a dominant Manchester City a 1-0 win at Chelsea.
Jesus settled a tight affair when his 53rd-minute effort took a touch off Jorginho to beat Chelsea keeper Edouard Mendy as the Blues lost for the first time this season.
Jesus almost added a second when Thiago Silva cleared his effort off the line while Aymeric Laporte should have scored but somehow slid a shot wide from inside the six-yard box.
Mendy also produced two crucial saves from Jack Grealish to keep the scoreline low.