The Saints fought back from a first-half deficit but the hosts grabbed a late leveler thanks to the ever-influential Maloney
Wigan had taken the lead when Gary Caldwell headed home unattended from a corner, but it was unable to hold onto its advantage as second-half strikes from Rickie Lambert and Morgan Schneiderlin looked to have sealed an important three points.
Maloney had the last laugh though, as he turned home from a right-wing corner to share the spoils.
Despite a bright opening to the game, both sides looked tentative in the final third and were unable to find a telling pass in key areas.
It was a scrappy beginning in truth with stray passes aplenty, with both Roberto Martinez and Mauricio Pochettino clearly aware of each other's passing philosophy as both sides closed one another down with intent.
The first real opening of the contest fell to the home side, though, with Di Santo coming close to capping off a flowing move, but could only steer his effort straight at Artur Boruc.
Southampton then mustered up a chance of its own but Ramirez incredibly missed a gilt-edged opening. After the Saints stole the ball in midfield, they broke with purpose, and when Lambert found the Uruguayan with a stunning cross, he must have envisaged a flag being raised, as he blazed over the bar on the volley with no one surrounding him.
The opening goal arrived after 26 minutes as captain Caldwell rose unmarked to nod home from a Beausejour corner.
The marking from the visitors was questionable as Maya Yoshida allowed the Scot to go unchallenged and have the simplest of tasks to glance home past Boruc.
There was nothing stylish - as Martinez wants his sides to play - about the goal but the importance of the goal in a battle of the basement boys like this was never to be under-estimated.
The Latics hard work to find the opener was almost undone within a matter of seconds as McCarthy's clearance rebounded off Morgan Schneiderlin and went cannoning towards Ali Al-Habsi's goal, but the Oman stopper recovered to tip wide.
Despite the lead, the Latics fans were not happy at the scrappy nature of some of their team's passing but they would have been more annoyed had Jos Hooiveld nodded home from a Schneiderlin corner as the Saints stepped up the pressure prior to the break.
The second half started much like the first - in a cagey manner - as Southampton plotted a way back into the game.
Pochettino threw on both Steven Davis and Adam Lallana early in the second half as he sought to gain some possession of the ball back, with Wigan all of a sudden starting to go onto the back foot and defend deeper.
They were duly punished. Mid-way through the second-half Cork found himself in space and picked out a delightful cross which Jay Rodriguez flicked on for Lambert, who snuck in behind the defense to head home past a despairing Al Habsi.
Southampton continued to up the ante, with the Latics keen to exploit the visitors on the counter, but Lallana struck the post after hesitancy in the Wigan backline, before Luke Shaw's dizzying run and cross teed up Lambert at the far post who went for the spectacular volley, but could only guide his shot wide.
The Saints applied serious pressure to the Wigan goal, but the home side always looked a threat with Maloney and Callum McManaman - introduced for Roger Espinoza - broke with pace down the flanks and it almost produced a winner.
The former picked out a cross from the left which narrowly evaded everyone before James McArthur came within inches of applying a finishing touch, only to find Shaw in place to knock out for a corner.
The visitors would not go down without a fight, though, and stole what looked to be a winner that had been richly deserved for their second half endeavors.
Rodriguez escaped down the left-hand side and waited for a willing runner in the center - Schneiderlin obliged as he met the low cross and tapped home beyond a statuesque Al-Habsi to send the Saints fans behind the goal into raptures.
To their horror, though, they were unaware of what would happen next. Set pieces appear to be the undoing of the Saints this season and two within one game proved where Pochttino must focus his training on next week.
A corner from the right was flicked on by Paul Scharner and at the back post lurking was Maloney, who turned home into the far corner past the dive of Boruc.
All in all, the point was probably a fair reflection of the contest but the Saints will surely be wondering what might have been if they could defend set-pieces.