Paul Jewell's return to the JJB Stadium ended in defeat as second half goals from Paul Scharner and Antonio Valencia gave Wigan all three points.
Paul Scharner set Wigan on their way to a 2-0 win over Derby
Scharner pounced on the hour mark to turn the ball in at the far post after Emile Heskey's close range effort was parried by Derby keeper Roy Carroll.
Valencia wrapped up the points six minutes from time, crashing a shot into the roof of the net from six yards out.
The result moves Wigan up three places to 14th while Derby remain bottom.
The Rams have now gone a club record 21 league matches without a win and are heading ever closer to the Championship.
It was the visitors who managed the first effort on goal after six minutes, Stephen Pearson shooting straight at Wigan keeper Chris Kirkland from the left hand side of the 18 yard box.
Wigan responded when captain Mario Melchiot delivered a perfect inswinging cross to Kevin Kilbane, but the midfielder headed straight at Carroll who gathered the ball at the second attempt.
All the focus before the game had been on Jewell's return to the club he quit in May after six years in charge.
And he enjoyed his fair share of luck in the first half as the home side dominated the opening 45 minutes.
Melchiot was denied a 25th-minute opener when Giles Barnes appeared to clear the defender's five-yard back-heel from behind the goal-line.
Replays showed the whole of the ball had crossed the line but the officials waved play on.
After Emmerson Boyce required a shirt change due to a nose bleed, another officiating decision potentially robbed Wigan of the opening goal.
A through ball from Emile Heskey into Marlon King should have sent the striker clear, and although he was onside by a yard, the linesman who failed to spot the earlier 'goal' raised his flag.
Derby arrived without a win on their travels this season and offered little threat at all.
But their stubborn resistance lasted for 60 minutes, until Scharner scored his fifth goal of the season.
Carroll made a fine double save to palm out Heskey's header and then tip away the striker's follow-up but could do nothing about Scharner's far-post effort.
Melchiot was close to making it two in the 80th minute as his header from a Kilbane corner flashed wide, before Valencia sealed Wigan's second successive home win.
• Wigan boss Steve Bruce:
"The mentality was good, but it was never going to be easy on this pitch.
"We made hard work of it and needed a break but once we got the first goal we were comfortable.
"It's going to be tense now for everyone down the bottom but thankfully I've got some experienced players here who've been down there before."
• Derby boss Paul Jewell, apparently resigned to his side's fate:
"I'm embarrassed at the way we played. I can accept losing but not like that, it was a disgrace.
"Some players are not worthy of being here and the sooner we can get them out the better.
"We've got to do some wheeling and dealing to get this team back in the Premier League."
Wigan: Kirkland, Melchiot, Boyce, Scharner, Edman (Koumas 90), Valencia, Brown, Palacios, Kilbane, Heskey (Bent 90), King (Sibierski 85).
Subs Not Used: Pollitt, Bramble.
Goals: Scharner 60, Valencia 84.
Derby: Carroll, Leacock (Todd 46), Stubbs, Moore, McEveley, Fagan, Ghaly (Sterjovski 62), Savage, Pearson (Villa 57), Barnes, Miller.
Subs Not Used: Price, Lewis.
Ref: Alan Wiley (Staffordshire).
BBC Sport Player Rater man of the match: Derby's Kenny Miller on 7.23 (on 90 minutes).
• Please note that you can still give the players marks out of 10 on BBC Sport's Player Rater after the match has finished.