Steve McClaren's in-form side, who were already the highest-scoring team in the division, raced into a three-goal lead inside 29 minutes at the DW Stadium on Sunday.
On-loan Manchester United youngster Nick Powell pulled one back for Wigan five minutes into the second half, but Derby held firm thereafter and now sit fifth, having claimed more away points than any side in England's second tier this season.
By contrast, Wigan have now suffered three home defeats in succession - one of those coming to Zulte Waregem in the UEFA Europa League - and remain 14th.
Craig Bryson opened the scoring after just three minutes, curling home a 25-yard free-kick after Simon Dawkins had been brought down.
Dawkins doubled the visitors' lead in the 15th minute when a pass deflected into his path and it was not long before Derby had a third goal courtesy of a Chris Martin penalty.
The forward was upended by James McClean and sent Lee Nicholls the wrong way with the resulting spot-kick.
Stephen Crainey hit the crossbar for Wigan at the end of the first half and Owen Coyle's men were much improved after the interval.
Powell headed home an Emmerson Boyce cross to reduce Derby's lead, but Wigan could not find another goal despite piling on the pressure.
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