Saints substitute Charlie Austin headed the late winner on his debut as Southampton won at Old Trafford for the second season in a row and left Louis van Gaal facing fresh questions about his future.
In a dour game of few chances, Austin rose to nod home a James Ward-Prowse free-kick three minutes from time and sink a lacklustre and impotent United at Old Trafford.
Wayne Rooney, looking to score for the fifth successive game, had the first sight of goal on 20 minutes when he picked up the ball from Ander Herrera and fizzed a low effort narrowly wide.
Southampton were a threat on the counter, though, and went close through Victor Wanyama whom headed over at the far-post from Jordy Clasie's free-kick.
The best chance fell to reported United target Sadio Mane 10 minutes before the break as Dustan Tadic played him through, but he failed to control the ball and David de Gea gathered.
Van Gaal introduced Juan Mata at the break and the change seemed to give the side another gear as Cameron Borthwick-Jackson's dangerous cross evaded everyone before Anthony Martial was unlucky not to latch on to Mata's pinpoint pass.
Matteo Darmian blocked well from Mane- picking up a heavy knock in the process- before Shane Long and Wanyama both went close in quick succession with deflected headers.
Southampton were beginning to sense victory in the offing and sent on the added threat of Austin in place of Mane, as United introduced the returning Adnan Januzaj for the closing minutes.
Both players were to play a part in what proved to be the Saints winner as the young Belgian needlessly gave away a free-kick, and Austin headed home from the resultant delivery with his first touch in a Southampton shirt.
That knocked the stuffing out of United as Januzaj fired a late effort wide, meaning Southampton are now unbeaten on their last three Old Trafford visits.
Overall team performance: I'm not even going to bother.
United Faithful Man of the Match.... er... Juan Mata only came on at half-time but did at least try to get the team going with some nice passes