Inspired substitutions by Ipswich boss Joe Royle paid off handsomely as ex-Town boss George Burley suffered another losing return to Portman Road.
Town ran out 2-1 winners in the league against Derby in Suffolk a month ago and won more easily this time with three second-half goals.
The game got off to a lively start with Marcus Tudgay seeing a shot deflected narrowly wide for Derby while Darren Bent twice and Jermaine Wright all went close for Town.
The hosts also felt they could have had a penalty when Youl Mawene, who scored an own goal in the league game here, appeared to handle a Matthew Richards cross.
Home keeper Kelvin Davis saved smartly from Luciano Zavagno and then excelled to tip over a venomous Lee Morris drive as Derby threatened.
The visitors had their own penalty shout rejected when the ball bobbled up onto Richard Naylor's arm but it appeared accidental.
Both sides had good chances to score before half time, Pablo Counago heading wide for Town from a good position while Mawene nodded over from close range after an Adam Bolder corner.
Ipswich went ahead on 54 minutes when substitute Jim Magilton, with his first touch, lofted a free kick to the far post where Naylor glanced a header home.
Another substitute, Shefki Kuqi, put Counago in but his shot was too close to Lee Grant.
The pair teemed up again on 69 minutes for the second goal when Counago freed Kuqi down the wing and he picked out Tommy Miller who fired low into the corner.
Derby had chances to make a game of it, debutante Manuel Fernandez outjumping Davis to head against the bar and the keeper also denied the Spaniard when he broke through.
Town rubbed salt in the wounds a minute from time when Grant spilled a Martijn Reuser cross and Kuqi tapped in from almost on the line.