Billy Davies' Forest were on a seven-match unbeaten run on home turf but were blown away by the Latics, who were inspired by on-loan Leicester man Martyn Waghorn.
Waghorn put the visitors into the lead in the first half before setting up a goal for Emmerson Boyce in the second, after Jamie Paterson had fired the Reds level.
A spectacular third goal from James McArthur looked unlikely to be beaten for quality, until Jordi Gomez smashed a breathtaking 20-yard shot high into the corner of the net in the 90th minute.
It was enough to secure a big three points for Wigan, who climbed up into the top six, while leaving injury-hit Forest trailing second-placed Burnley by 11 points.
Danny Fox came perilously close to an own goal as he headed over his own bar while trying to divert a flicked effort from Nicky Maynard away from the target.
A perilous piece of defending from Leon Barnett at the other end then almost gifted Forest the opener as Leon Barnett's short back pass sent Simon Cox racing clear, but the striker could not connect properly with his shot as Ali Al Habsi raced quickly off his line.
It was not a shock when the visitors did edge their way into the lead in the 35th minute following a spell of pressure.
A driven shot from Gomez was well blocked, but after taking more than one deflection, the ball fell kindly for Waghorn, who - with Darlow having dived to save Gomez's effort - was left to slot into an empty net.
Jamie Paterson was a whisker away from levelling as the Wigan defence backed off, lashing a fierce shot just over the angle of post and bar.
And the second half also began with an opportunity for Forest, as Mackie fought his way into the penalty area from the right but saw Al Habsi make a smart save, from his low shot, at the near post.
Mackie was to be the catalyst for the Forest equaliser in the 54th minute, as he again fought his way into space down the right before delivering a low cross. Cox's clever lay-off in the centre found Paterson, who drove an unstoppable rising shot high into the back of the net.
The sides were level for only 12 minutes, however, before Boyce flicked the visitors back into the lead. A Waghorn volley was already arrowing towards goal before the defender got a touch with his head to steer it beyond Darlow.
And the keeper was beaten again in the 71st minute as another deflection helped Wigan's cause. This time it was a shot from McClean that was charged down but fell kindly for McArthur, although there was little luck involved as he then smashed a low shot across goal and into the bottom corner with supreme precision and power.
Gomez then made it 4-1 in the last minute of normal time, sending a superb bending shot high into the corner of the net from the edge of the box.