Man Utd were left frustrated at St Mary’s as Jannick Westergaard’s header secured a point for Southampton, who played the final 20 minutes with 10 men.
Daniel James opened the scoring early in the first half, cutting in from the left and smashing the ball past a helpless Angus Gunn into the top corner.
Southampton caused some problems with their high press but forwards Che Adams and Danny Ings grew more and more isolated, in a comfortable first half for United.
The Saints came out a different team after the break, with Che Adams screwing a shot just wide before Jannick Westergaard levelled the scores.
The Danish international out-jumped Victor Lindelof and placed his header past David De Gea, to score his first goal for Southampton.
The game changed midway through the second half when Kevin Danso was shown a second yellow card for a rash challenge on Scott Mctominay.
James immediately tested Gunn with another stinging shot before fluffing two further chances.
United had further chances to secure all three points with Marcus Rashford and Jesse Lingard wasting opportunities.
17-year-old Mason Greenwood came on for the last 10 minutes and nearly stole the headlines but his curling effort was palmed wide of the post by Angus Gunn.
Southampton deservedly held on for the point.