A Robin van Persie hat-trick saved the day for United, and the striker also missed a penalty when he tried the Panenka dink.
Rickie Lambert and Morgan Schneiderlin scored for Southampton as they looked for their first league points of the season, but they were to be denied in dramatic fashion.
Here, Sports Mole dissects Ferguson's 599th league win in his 1000th game in charge of the Red Devils.
On target: 4
On target: 7
Was the result fair?
No. The result, especially the manner in which it came, was very harsh on Southampton as they dominated the game at times. While they were ahead, they deserved their lead, and while United were by no means overrun by Nigel Adkins's men, they couldn't control them at times either. A draw probably would have been the most fair result, but you won't find many neutrals who would've begrudged Southampton the win.
Very good. Adkins will be delighted with his side, if distraught at the result. They deserved at least a point from the match, but still find themselves looking to get off the mark in the league. If they perform like this more often, however, then it won't be long.
Manchester United's performance
A win is a win at the end of the day, but Ferguson will have seen his side perform better in his 1000-match reign. They weren't in full flow by any means, but they weren't terrible either. Still, Fergie knows that improvement will be needed - Van Persie can't save them every week.
Sports Mole's man of the match
It has to be Van Persie really. Until the Dutchman saved his side, it would have been Rickie Lambert or Adam Lallana, who both performed superbly to get Southampton ahead, but you just can't ignore a hat-trick hero. His penalty was a major blip, but it's fair to say he redeemed himself.
It has to be Van Persie's penalty. The former Arsenal man is usually so clinical from 12 yards, but this time tried to be cute and chip the ball past Kelvin Davis. It was a poor effort, however, and Davis comfortably saved.
Mike Dean didn't have too much to do, but got the one big decision spot on. Hooiveld's lunge through the back of Van Persie was definitely a penalty, and Dean was quick to point to the spot. Also a good decision to only give the defender a yellow card when others may have sent him off.
Southampton: Things don't get much easier for Southampton in their quest for a first point of the season - they travel to the Emirates to face Arsenal after the international break on September 15.
Manchester United: United return to Old Trafford after the international break, playing Wigan on September 15 before hosting Galatasary in the Champions League on Wednesday 19.