Jay McEveley and David Martin scored the goals in the second half.
McEveley struck three minutes after the break, powering a close-range header past Peter Enckleman from Kris Commons' inswinging free-kick.
Martin doubled Derby's advantage in the 63rd minute when he raced clear down the left side of the area and sent a low shot into the far corner.
The likes of Stephen Bywater, Paul Green, Stephen Pearson, Rob Hulse and Chris Porter have joined the Rams' lengthy injury list recently, so Dean Moxey, Ben Pringle and Martin were handed rare starts.
Kris Commons made his first appearance for over two months following a hamstring problem, while youngsters Mark O'Brien, Callum Ball, Ryan Connolly and Jeff Hendrick were named on the bench.
Cardiff boss Dave Jones made nine changes as he rested key players ahead of the play-off semi-final against Leicester.
Tony Capaldi and Kelvin Etuhu were the only survivors from last weekend's home win over Sheffield Wednesday.
Commons should have put Derby ahead after only 40 seconds. Robbie Savage slipped Nicky Hunt in behind the Cardiff defence and his low cross from the right was steered wide by the Scotland international from 10 yards out.
There was little else in the first half to warm the hands of the 31,102 inside Pride Park.
Ross McCormack's curling free-kick was pushed over the crossbar by Saul Deeney after 14 minutes before the same player flashed a shot narrowly wide just before the break.
In between, Tomasz Cywka worked Enckleman with a low shot after winning back possession on the edge of the Cardiff area.
In stark contrast to the previous 45 minutes, the start of the second half was much more entertaining.
McEveley broke the stalemate and soon afterwards Commons spurned another opportunity from 10 yards out after reacting quickest the rebound following Enckleman's save to deny Michael Tonge.
Martin made it 2-0 just after the hour mark and, with the game won, Derby manager Nigel Clough handed first-team debuts to Ball and Connolly.
McCormack always provided the biggest threat for Cardiff and the Scotland international forced a superb save from Deeney late on.
His 25-yard shot clipped the top of the crossbar via the fingertips of the Rams keeper with three minutes remaining.