Marcus Rashford came back into the side for Ole Gunnar Solskjaer after recovering from injury, but it was Southampton who took the lead, surprising the crowd. Yan Valery scored a brilliant goal, thrashing the ball from outside the box. David De Gea could have stopped it, but no credit should be taken away from Valery.
Andreas Pereira bettered Valery's effort in the second half. The youngster let rip from far to equalise for United. Soon the home side were in front, as Romelu Lukaku scored with a low drive into the far corner. It looked as though United were on course, but James Ward-Prowse played spoilsport. He curled in a magnificent free-kick to make it 2-2.
Lukaku had the last laugh though, when he curled in a right-footed shot to give United the win in the dying minutes. Southampton conceded a penalty in stoppage time, but Paul Pogba's effort was saved by Angus Gunn.
It was an entertaining game at Old Trafford, as Manchester United set themselves up nicely for the Champions League tie against PSG in midweek. Here are the major talking points from the game.
#5 No return for Southampton despite a plucky performance
One thing is for sure: Southampton did not make it easy for Manchester United. They took the lead in the first half and equalised later to make it 2-2. United had more possession, but they created 7 chances in the game, the same as the Saints.
The performance should give them confidence, but not getting any points would be a bummer. Ralph Hasenhuttl's side is two points clear of the relegation zone at this moment. Cardiff City are behind them in 18th place, as both Fulham and Huddersfield have all but accepted their fate. Essentially, Southampton are fighting to avoid finishing in 18th place.
The Saints' schedule is relatively easy, and the last stretch looks extremely favourable. They do have some injuries to deal with, but Hasenhuttl will feel that the quality of his side should see him through.