The last time the Owls played at Pride Park, they came back from two goals down in dramatic circumstances to salvage a point.
But on this occasion, the result was never in doubt once the home side had taken the lead through Jake Buxton moments before the interval.
Further goals from Will Hughes and Chris Martin ensured three points for the hosts, who were dominant from the first whistle and good value for victory.
The Rams asked more of the questions in the early exchanges although Chris Kirkland was untroubled in the Wednesday goal.
The keeper, though, was left powerless and wrong-footed on 16 minutes when a Craig Bryson free kick took a wicked deflection and fizzed narrowly wide.
Simon Dawkins then sent a drilled shot goalwards that Roger Johnson blocked as Derby took a foothold on the game.
Dawkins had a golden chance moments later but dragged wide after finding space in the box before the contest reverted to type, with the Rams knocking on the door and Wednesday holding firm.
It was more of the same as half time approached and for all the paucity of play in their opponents’ half, the Owls were resolute at the back as they largely frustrated the Midlanders.
But right on the whistle, the hosts took the lead – a strike that would open the floodgates.
Jamie Ward sent an accurate corner into the mix and Buxton was on hand to send a powerful header into the net from the underside of the crossbar.
Almost immediately after the resumption, the Rams made it two.
Wednesday lost possession in midfield and so began a swift five-man move that ended with Hughes ghosting in at the far post to slot past Kirkland.
That gave the Owls the proverbial mountain to climb but no sooner had they motioned a move to that end, the game was all but over.
Derby pressed forward and the ball found its way to the right channel into the path of Hughes, who crossed for the onrushing Martin to prod home from close range.
Wednesday made a double substitution, with Jermaine Johnson and Giles Coke introduced to spark some life into what was a lacklustre performance from the visitors.
But the damage was done and although the Owls crept back into proceedings in part through the remainder of the game, the outcome was never in doubt.
Derby: Grant, Forsyth, Bryson, Keogh, Martin (Sammon 85), Ward (Davies 90), Hughes, Buxton, Dawkins (Bennett 76), Wisdom, Cisse
Owls: Kirkland, Buxton, Zayatte, Roger Johnson, Reda Johnson, Antonio, McPhail (Coke 53), Olofinjana (Palmer 73), Helan (Jermaine Johnson 53), Fryatt, Wickham