The Latics could have booked their place in the top six with a victory, but Uwe Rosler's men were below-par across the board and squandered an excellent opportunity to take the lead when Martyn Waghorn saw his penalty saved midway through the first half.
Goals after half-time from Andy Keogh and Stephen Dobbie sealed victory for the visitors, who completed a double over their Lancashire rivals.
Latics boss Rosler had reverted to the same team that convincingly beat Reading on Good Friday, and the initial signs were that a similar result would be forthcoming.
With Shaun Maloney pulling the strings, the Latics dominated the opening quarter and ought to have taken the lead but for Waghorn fluffing his lines from 12 yards.
After Maloney was adjudged to have been fouled inside the penalty area by Tony McMahon, Waghorn saw a decently struck penalty well saved by Matt Gilks, who flew across to his left to divert the ball to safety.
Waghorn's afternoon got worse moments later when he completely missed his kick right in front of goal after good work from Roger Espinoza.
And Wigan almost paid the price when Blackpool came desperately close to taking the lead on the stroke of half-time.
Chris Basham got into a good position down the right and narrowly failed to find Neal Bishop, who would have had a tap-in from close range.
But the home side did not make the most of their break and fell behind to Blackpool's first real effort on target just before the hour mark, with Keogh heading home after a good run and cross from Isaiah Osbourne.
Wigan tried for an immediate leveller but Nick Powell could only head wide while Maloney sent a free-kick just over the top.
And it was game over in the 70th minute when Dobbie made it 2-0 to the delight of the 3,500 away fans behind the goal, finishing superbly at the far post from Keogh's cross.
Not even the introduction of Powell, Marc-Antoine Fortune and James McClean off the bench could lift the home side, who will travel to struggling Birmingham for their game in hand on Tuesday night.
Powell flashed a late shot over for Wigan, but it was an afternoon to forget for last year's FA Cup winners.