The visitors started the game strongly and Roger Espinoza latched onto a throw-in from Maynor Figueroa. He was allowed space and time to drill at volley at goal, but Jack Butland was on hand to make the stop.
Wigan continued to have the better of the opportunities in the first half as they frustrated the home side, and Adam Forshaw's drive from 25 yards went just over the bar, with Butland scrambling.
Uwe Rosler's men went close again as Callum McManaman fired an effort at goal from close range, but Butland came out to narrow the angle and made an impressive block with his body to keep the scores level.
Wigan were handed a glorious chance to take the lead just before the break when John Eustace was adjudged to have handled the ball inside the area. James Tavernier took the spot kick, but saw his effort saved by Butland.
Derby immediately raided downfield and won a free kick from which Johnny Russell lifted a dangerous cross into the area for Eustace to volley into the net.
After the break, the Rams began to dominate possession and Jeff Hendrick drilled an effort at goal from distance which Scott Carson had to be at his best to palm away from goal.
Steve McClaren's side nearly added a second when Chris Martin caused havoc in the penalty area and managed to find Craig Bryson with a cutback, but the midfielder's effort was deflected wide of the target.
Wigan found an equaliser against the run of play in the 69th minute when Espinoza raided down the right and spotted the run of McClean with a cutback, and the winger bundled the ball into the net.
McClean scored his second and the winner late in the game after Butland had denied Forshaw. Marc-Antoine Fortune's follow-up effort was blocked into his path, and he slotted the ball into the net.