Villa striker Bent went down at the DW Stadium clutching his ankle following a challenge by Antolin Alcaraz and it was immediately obvious he could not continue.
The injury will almost certainly rule him out of England's midweek friendly with Holland, and possibly a lot longer given the pain he was in.
It was an incident which overshadowed a curious game, which Wigan dominated but Villa had the best chances, Ali Al Habsi called upon three times to keep the hosts level.
Hugo Rodallega came closest for Wigan in a frantic finish.
It was not enough to give the Latics their second home win of the season though, or take them off the foot of the Premier League table.
However, it was the Villa fans who booed their team off at the end, their patience with Alex McLeish starting to wear very thin.
The first-half was a microcosm of Wigan's season in that despite enjoying long periods of possession, it was Aston Villa who carved out the better chances.
In his final game before returning to MLS, Robbie Keane tried his luck from 25 yards with a low daisy-cutter that looked harmless when it left his foot, but was actually destined for the bottom corner until Al Habsi pushed it away.
Shortly afterwards, Keane turned provider, lifting a deft pass beyond a static Wigan back four.
Bent had the pace to reach it. Unfortunately for the England man, he could not beat Al Habsi either as his shot cannoned away off his knee.
Stephen Warnock also flashed a shot wide in what was an brief period in the ascendancy for the injury-hit visitors, who had named Gabriel Agbonlahor as skipper for the first time.
In contrast, Wigan controlled proceedings as much as it was possible to do on a pudding of a pitch, causing difficulties for both defences.
The arrival of Jean Beausejour from Birmingham during the transfer window has provided the Latics with a welcome cutting edge
It was the winger's deep cross in the early moments that Gary Caldwell lifted on to the roof of Shay Given's goal.
Carlos Cuellar did well to get a similar effort out of his six-yard box before Emmerson Boyce arrived to do some damage.
Had Wigan been caught napping right at the start of the second period, manager Roberto Martinez would not have been impressed.
Al Habsi was once again equal to the threat though after James Collins had turned the ball back into the Wigan box and, from Caldwell's flick,
Cuellar thundered a header goalwards.
Quickly though, Wigan got themselves on top once more.
Beausejour was proving particularly difficult to pin down and on three occasions it was his crosses that brought peril for Villa, whose supporters were starting to get increasingly agitated at the lack of invention from their team.
Di Santo had a penalty appeal correctly waved away by referee Kevin Friend as his shot struck Collins and then Albrighton.
The introduction of Wigan old-boy Emile Heskey for Albrighton sent the anti-McLeish sentiment into overdrive.
Wigan appeared incapable of taking advantage though. Two corners were curled straight out of play before one of the culprits, Moses, sprinted clear down the right only to drill his cross beyond an empty six-yard box.
Bent's injury drew a temporary halt to proceedings.
Even though there was no booking for Antolin Alcaraz's foul on the England striker, it was immediately obvious he was in some distress and the sight of him being carried down the tunnel was not good.
When play eventually resumed, Hugo Rodallega turned on to a pass from fellow substitute Mohamed Diame and curled narrowly over, then Emmerson Boyce dashed back to clear just as Keane was about to pull the trigger.
Charles N'Zogbia might have caused a problem for his former club near the end, although Di Santo had the last chance, which was repelled by Given.