Mark Viduka showed just why Middlesbrough are desperate to tempt him with a new contract when he hit the winner - his 12th goal of the season.
It ended any doubt about Boro's status next season and stretched the Latics' run to eight games without a win.
Paul Jewell opted for a shake-up bringing in Mike Pollitt for his first start of the season, and preferring Julius Aghahowa as the strike partner for Emile Heskey.
The back four also had a new look with Paul Scharner and Emmerson Boyce the central defenders. Antonio Valencia returned after a three-match ban.
Boro left striker Yakubu out after a run of 11 games without a goal, and gave Dong-Gook Lee only his second start.
Wigan carved out the first chance after 17 minutes following a mis-hit shot by Denny Landzaat. It found Valenicia who squared for Ryan Taylor to hit an excellent cross to the back post. Lee McCulloch powered in the header only to see it clip the crossbar.
There was concern for the Latics when Taylor was pole-axed in a clash of heads with Emanuel Pogatetz but he was okay after lengthy treatment.
Wigan then found that their luck was right out when Leighton Baines was penalised just outside the area for a foul on Lee.
One time Wigan target Stewart Downing slipped as he took the free-kick - earning jeers from the home fans - but the sliced shot found its way to Viduka who stole in at the back to shoot Boro into a 29th-minute lead.
Pollitt then came to the home side's rescue, denying Boro a second when he beat out a shot from Downing who had beaten the offside trap.
Wigan appeals for a penalty after Andrew Taylor appeared to handle the ball failed to impress ref Mark Clattenburg and a Heskey header brought the first save from Mark Schwarzer in added time.
Boro threatened again early in the second half when Downing lashed wide when the unmarked Viduka was screaming for the ball.
Aghahowa forced Schwarzer into action before Boro appealed in vain for a penalty when Lee went down in the box.
Wigan battled away but the closest they came was a Taylor free-kick that flew just inches wide.