Di Santo double gives Wigan points
Di Santo - tripling his total of goals for the club to only three goals in 32 appearances since joining from Chelsea last August - struck in each half to give Wigan their first win of the season after two draws.
Defeat brought QPR, being watched by new signing Joey Barton from the stands, back down to earth after their away win over Everton last weekend.
Di Santo, who had an earlier effort well saved by Paddy Kenny, produced a strike to remember for his first as, set up by the industrious Hugo Rodallega, he teed the ball up and volleyed past Kenny to give the hosts the breakthrough goal
Woodwork saves Wigan
The goal had been coming in a highly entertaining first half, with both sides having chances before the 22-year-old Argentinian's finish to break the deadlock.
Victor Moses had missed early on for the hosts but it was QPR's most prized asset, Moroccan Adel Taarabt, who went closest with a beautiful effort which beat Ali Al Habsi but came back off the bar.
Al Habsi - whose outstanding performances for Wigan last season contributed hugely to their staying up - had also been forced into a stunning save from veteran midfielder Shaun Derry and then reacted brilliantly close to half-time to tip Taarabt's deflected free-kick onto the post.
The hosts had the better chances in the second half as the visitors had little to offer, and former Republic of Ireland international goalkeeper Kenny had to be at his best to deny the marauding Di Santo.
Di Santo seals victory
However, Kenny could do nothing about Di Santo's second strike in the 66th minute as the Argentinian cheekily took the ball off the toes of Rodallega and made no mistake as he powered the shot into the top corner.
QPR responded in plucky fashion - Bruno Perrone's header beat Al Habsi but cannoned back off the bar, while the Wigan goalkeeper was then at his best when he touched over Taarabt's free-kick as the clock wound down.