It looked like it would be a very good day for the Latics when Gary Caldwell headed them into the lead in the 25th minute but Southampton were a constant threat and it was no surprise when Rickie Lambert levelled 64 minutes in.
The visitors then thought they had won it as Morgan Schneiderlin finished off a break five minutes from time but there was a sting in the tail as Maloney prodded in from a corner.
Southampton really should have scored in the 16th minute as Lambert picked out Gaston Ramirez in acres of space 10 yards out. With the DW Stadium waiting for an offside flag that never came, Ramirez slashed the ball well over the bar and replays showed he was clearly onside.
The next opening produced a goal, with Jean Beausejour the architect. The Chilean's corner picked out the head of Caldwell, who, having engineered space, placed his header perfectly into the bottom corner.
The scoreline was harsh on Saints and they dominated the final stages of the first half but were unable to find an equaliser. Visiting boss Mauricio Pochettino made a change at the break, Steven Davis replacing Ramirez, who had picked up an injury at the end of the first half in a clash with Roger Espinoza.
The visitors continued to do most of the pressing and with a little over half an hour to go Wigan boss Roberto Martinez opted for a defensive reshuffle. Jordi Gomez replaced Ronnie Stam, meaning Beausejour dropped back into defence, Maynor Figueroa moved into the centre and Paul Scharner to right-back.
In the 60th minute, Adam Lallana entered the fray for Saints as he continued to work his way back from a knee injury and four minutes later they had their equaliser. Jack Cork crossed and Jay Rodriguez outjumped the Wigan defence to head on for Lambert, who bravely beat Ali Al Habsi to the ball at the back post.
Southampton sensed a vital win was there for the taking and they were inches away from going ahead in the 71st minute as Lallana pounced on a half-blocked effort and smacked his shot against the near post.
Southampton were not to be denied and, from a Latics corner, Rodriguez burst away down the left, beat a lunging challenge from substitute Callum McManaman and crossed for Schneiderlin to smash home. Wigan refused to be beaten and with the match entering the 90th minute Scharner got his head to a corner and Maloney scuffed the ball over the line.