After creating clear-cut chances towards the end of the first half and continuing the form into the second period, Wigan finally went ahead through James Perch’s fine volley.
But it was the first of three goals in the space of five minutes as Rovers equalised through Ben Marshall’s first after 53 minutes, which was a wonderfully directed long-range effort.
Jordan Rhodes put them ahead three minutes later with a close-range header, and Marshall curled in a second after 81 minutes to round off a fine spell of supremacy which saw Scott Carson make saves from Luke Varney and Marshall.
It could have been so different though had Ivan Ramis not blasted over a penalty in the first half when Callum McManaman went down under an Alex Baptiste challenge, but Wigan were overwhelmed despite McManaman forcing Paul Robinson into a first-half save.
The result leaves Rovers undefeated at Ewood this season in the league, and continues Wigan’s woeful record at Blackburn, where they have won once in 11 visits in all competitions.
Gary Bowyer included the fit-again Rudy Gestede, while Uwe Rosler handed debuts to Andy Delort and William Kvist.
Wigan controlled much of the early exchanges, with Emmerson Boyce heading wide from a corner, but neither side had a clear chance until a moment of controversy after 37 minutes.
McManaman went down under pressure from Baptiste and referee Roger East pointed to the spot even though replays suggested the Wigan man was looking for contact.
Justice was served though as Ramis blazed the penalty over.
McManaman remained in the thick of the action and forced a fine save from Paul Robinson in first-half injury time and then crossed for Boyce who headed over when well placed.
The visitors eventually made the most of their pressure six minutes into the second half as an Emyr Huws cross was cleared as far as Perch whose low volley through a crowd of players beat Robinson.
But Rovers hit back within two minutes thanks to the exquisite strike from Marshall who arrowed a 25-yard strike into the bottom corner beyond the stranded Carson, and they completed the turnaround three minutes later when Rhodes headed past Carson to find the net for the third consecutive game.
Carson then made a superb one-handed save to thwart Marshall’s curling effort after 70 minutes and Varney failed to get a telling touch on a superb team move with the goal gaping.
The Wigan stopper’s outstretched foot then denied Varney when clean through but Marshall put the game beyond doubt eight minutes from time with a beautiful curling effort from 25 yards.
Andrew Taylor lashed wide from 10 yards in injury time, and Wigan’s misery was complete.