The on-loan Reading winger hooked in a half-volley to put Alan Pardew's men in charge and they survived a late onslaught after Morgan Schneiderlin's 80th minute red card.
Southampton dominated the first half and skipper Jose Fonte fired just wide before Adam Lallana scuffed a golden chance straight at keeper Willy Gueret following Danny Woodards' slip.
Luke Chadwick sliced an attempted clearance onto his own crossbar as the Dons rode their luck before Antonio put the Saints ahead in the 26th minute. The 19-year-old latched onto Rickie Lambert's flick and fired a 15-yard half-volley in off the post for his second goal of the season.
The Dons improved after the break and Southampton keeper Kelvin Davis saved long-range strikes from Jermaine Easter and Jason Puncheon before Schneiderlin saw red for pushing Stephen Gleeson in the face.
Dons striker Aaron Wilbraham volleyed substitute Jude Stirling's cross against the post in a frantic finish, while Gueret tipped Lloyd James' strike wide at the other end in stoppage-time.