Title-chasing Wigan Athletic scored three second-half goals to inflict a 5-1 defeat on MK Dons at the DW Stadium.
The Dons were in with a chance at the break after Callum Brittain’s strike reduced the deficit following Will Grigg’s early tap in and Ethan Ebanks-Landell’s own goal.
However, Powell headed past Nicholls 10 minutes into the second period before former Dons striker Grigg completed a hat-trick with two quick-fire goals, condemning Dan Micciche’s men to a heavy loss in Greater Manchester.
The defeat, and results elsewhere in Sky Bet League One, ensures the Dons remain inside the bottom four, one point adrift of safety.
Boss Micciche handed Scott Golbourne his first start since New Year’s Day as one of three changes made to the starting XI. Golbourne, who missed four months of football due to a hip injury, was joined in defence by the available-again Elliott Ward with Kieran Agard the other addition to the side.
Peter Pawlett earned the Dons an early free-kick after he was upended, 30-yards from goal, following a strong run through the middle of the park. Chuks Aneke took the set piece but cleared the crossbar with his right-footed attempt.
Wigan threatened for the first time in the sixth minute when Nick Powell got behind the Dons’ backline but the linesman on the far side of the field raised his flag for a foul before the Latics midfielder could produce a save out of Lee Nicholls.
The Dons then went up the other end and won themselves a corner from which Aneke had an effort blocked. Moments later, Christian Walton raced off his line to beat Agard to a through ball.
It was a positive start from Micciche’s men but they were punished for a lapse in concentration on 11 minutes when Michael Jacobs got free and latched onto Powell’s pass. Jacobs waited patiently in the area before picking out the on-rushing Grigg, who tapped into the net from close-range. 1-0.
Grigg’s goal awoke the hosts, who looked eager to make up for their shock defeat to Portsmouth on Monday evening.
They went close to making it two soon after but Jacobs curled wide from the edge of the area. Dean Lewington then got in the way of an effort from Powell before Nicholls pulled off a stunning reaction save to deny Grigg from point-blank range.
Wigan eventually doubled their tally on 23 minutes when Powell’s in-swinging cross was inadvertently turned into the net by the head of a diving Ebanks-Landell. 2-0.
That goal left the Dons with a mountain to climb - a mountain which was almost made even bigger on the half-hour mark by Gavin Massey, who fired just wide of the left upright from the edge of the area.
Had Kieran Agard’s touch been better he may have been in with a chance of reducing the deficit within a minute - the link-up play was good but the striker’s control from Aneke’s pass let him down.
Ed Upson then curled wide from the edge of the D but it was with their next attempt, on 35 minutes, that they pulled a goal back. Aneke was the provider for Brittain, who created space on the edge of the area with a dummy and then drilled a low right-footed shot past Walton. 2-1.
The Dons went close to levelling just moments later but, from Golbourne’s corner, an unmarked Ward couldn’t keep his header down. Aneke then forced Walton into a diving save, with the loose ball almost landing at the feet of the on-rushing Brittain inside the six-yard box.
With the final chance of the first half, Walton denied Aneke again - the Wigan stopper claimed the forward’s header from Golbourne’s cross.
Wigan started the second period on the front foot and five minutes in it took a block from Ward to prevent Grigg threatening Nicholls. From the loose ball, the former Dons man fired high above the crossbar.
Soon after, at the other end, Aneke latched onto a cross from Brittain but couldn’t generate enough power in his strike to trouble Walton.
Lewington then got in the way of a low drive from Max Power, who later conceded a free-kick for a foul on Aneke. The Dons’ number 10 got his head to the resulting delivery from Upson but Agard couldn’t connect with the pass at the far post.
On 55 minutes, Nicholls produced a strong diving save to prevent Powell’s effort from sneaking in at the near post. Powell did, though, get the better of the Dons’ goalkeeper two minutes later as he climbed well to meet Massey’s ball in and send a looping header across goal, into the far corner. 3-1.
Micciche introduced Robbie Muirhead from the bench with 64 minutes on the clock and his first involvement was to deliver a well-placed free-kick into the area. His cross was a good one but the Dons were unable to fashion a shooting opportunity.
Thomas-Asante also entered play from the bench and his early direct run forced Dan Burn to concede a corner from which Ward had a header blocked by a Wigan defender on its way to goal.
The Latics then made sure of their victory with 15 minutes remaining - Grigg the goalscorer, latching onto a lofted through pass and finding the net courtesy of a lobbed finish which hit the underside of the crossbar on its way in. 4-1.
Grigg completed his hat-trick 60 seconds later, sliding in at the far post to convert from Jacobs’ low cross. 5-1.
That completed the scoring on a bitterly disappointing afternoon for the Dons in the North West.
Starting XI: Nicholls; Ebanks-Landell, Ward, Lewington (c); Williams, Brittain, Upson, Pawlett (Ugbo 81), Golbourne (Muirhead 64); Aneke, Agard (Thomas-Asante 70).
Unused subs: Sietsma, Wootton, Reo-Coker, Cisse.
Goal: Brittain (35)
Booked: Golbourne, Agard, Upson
Attendance: 8,404 (333 away)
Referee: S Stockbridge