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Jon Parkin put Preston ahead, but after a Billy Jones own goal, Derby exposed some alarming defending by scoring four after the interval.
Kris Commons gave Derby the lead in the 49th minute and although Chris Sedgwick levelled, a Rob Hulse double and a Shaun Barker header secured a third consecutive Championship home victory.
Chris Brown headed Preston's third in stoppage time but by then, the damage had been done.
Derby came into the game in good form at home but after a bright start, they went behind in the ninth minute.
A long ball from Preston's latest loan signing Tom Williams went over Jake Buxton and Parkin took a touch before firing low into the bottom right corner.
But despite that setback, Derby were putting the visitors under pressure and after several near misses, they equalised in the 34th minute.
It was tough on keeper Andy Lonergan, who made a superb save to parry Paul Green's volley, but the ball rebounded off Jones and went in.
Jay McEveley almost put Derby ahead a minute later with a spectacular strike from out on the left which Lonergan did well to tip against the bar, but Preston responded with a Parkin header that Green cleared off the line.
Derby started the second half as they had the first and from their 11th corner, the ball dropped to Commons who hooked it in from six yards.
The game was wide open and in the 62nd minute, Preston drew level when Parkin put Sedgwick in to place a low shot inside Stephen Bywater's right post.
But the visitors then collapsed defensively as Derby scored twice in the space of five minutes.
First Hulse was given too much time to bring the ball down before turning to volley past Lonergan from 14 yards in the 64th minute.
Preston's hopes of a comeback were crushed in the 68th minute when Barker was left unmarked at the back post to head in Commons' free-kick.
Another high ball in the 77th minute resulted in more chaos at the back as Lonergan dropped McEveley's deflected cross and Hulse bagged his second.