Goals from Heidar Helguson, Akos Buzsaky and Tommy Smith lifted Mark Hughes's QPR out of the Premier League relegation zone and left Wigan rooted to the bottom of the table.
Rangers were gifted the lead when James McCarthy handled in the area and Helguson converted the penalty.
Buzsaky fired home a stunning free-kick that went in off the post.
Rangers resolve encourages Hughes
A Hugo Rodallega free-kick pulled a goal back for Wigan before Smith sealed QPR's win with a long-range effort.
Victory was Hughes's first in the Premier League since taking charge at Loftus Road and only Rangers' second at home this season.
The three points lifts them out of the relegation zone and puts five points between them and Wigan, who remain bottom with only 15 points.
The visitors started the brightest as they fired in two excellent crosses from the left but Rodallega failed to get on the end of both.
Luke Young and Jamie Mackie then forced Wigan goalkeeper Ali Al Habsi into good saves as Rangers began to dominate.
Did you know?
The two previous times Rangers scored two goals at Loftus Road ended in defeat for the home side
And the hosts were gifted the lead after McCarthy inexplicably handled in the area as he defended a corner.
The referee immediately pointed to the spot to give QPR only their second penalty of the season.
Helguson stepped up and made no mistake beating the diving Al Habsi, who guessed the right way but could not keep the ball out.
Buzsaky then forced the Latics keeper into another save when he hit a long-range free-kick which was tipped just wide.
That should have served as a warning sign for Roberto Martinez's side but the Hungarian was given another chance moments later and this time he made no mistake.
Did you know?
Wigan are the lowest goal-scorers out of any of the 92 clubs in the Football League
This is the first time a meeting between the two sides has resulted in more than three goals
He curled a superb free-kick in off the post for his first goal since April 2011.
The goal gave him a real confidence boost and he forced Al Habsi into another superb save after the break.
However Wigan then began to look more comfortable and enjoyed more possession. They got back in it when they were awarded a free-kick in exactly the same place as Buzsaky had scored from in the first half.
Rodallega stepped up and curled the ball around the wall and into the top corner.
Conor Sammon went close for Wigan before Gary Caldwell conceded a second penalty for the visitors, pulling down Helguson just inside the area.
Martinez anger at 'shocking' penalty
The Iceland international took the spot-kick himself but Al Habsi guessed correctly for the second time and this time made the save.
Helguson then hit a stunning long-range dipping half-volley which went just wide of the right-hand post.
Wigan were continuing to press but their challenge ended when Tommy Smith scored with a wonderful strike.
The former Derby forward, on as a substitute at half-time, hit a shot from 25 yards out which flew into the top left-hand corner.
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