And they ended Chelsea's 11-match winning run stretching back to last season after keeper Petr Cech was sent off.
Roberto Martinez opted to make a couple of changes by giving starts to Jason Scotland and Paul Scharner, with Jason Koumas and Jordi Gomez on the bench.
Chelsea showed just one change with John Obi Mikel taking over from Michael Ballack.
The Latics had to weather a shaky opening few minutes but grew in confidence with Cech the busier of the two keepers in a lively first half.
Wigan struck after 16 minutes when Titus Bramble headed in from 12 yards when Hugo Rodallega fired in an inswinging corner from the left.
It was the big defender's first of the season and his fourth in Wigan colours.
The Latics were unlucky not to add to their lead when Scharner slipped at the vital moment with Scotland eyeing up the shooting chance.
And they went agonisingly close when Cech produced a stunning, top quality save to deny Emmerson Boyce from close range after England skipper John Terry had denied Scotland the chance of his first Premier League goal with a terrific tackle.
Chris Kirkland did well when dealing with shots from Michael Essien and Frank Lampard without too much difficulty and just before the break, Didier Drogba put one over the bar from 18 yards.
It looked ominous when Drogba embarrassed Kirkland with the equaliser 90 seconds into the second half.
But the writing was on the wall for the league leaders when Cech was red carded for a foul on Rodellega.
The Colombian rammed the spot-kick past stand in Henrique Hilario to register his third goal of the season and the Latics were back in front.
They had a couple of hair raising moments but Scharner made the win emphatic with the third in stoppage time after scoring at the far post from Maynor Figueroa's cross to make it an afternoon to remember.