Second-half goals from Dave Kitson and Shane Long settled an entertaining and closely contested game, to take Steve Coppell's side six points clear of the teams below them with two matches left.
Reading had won 4-0 at Pride Park on the final day of last season and they found the net twice in the first eight minutes only for an offside flag to cancel out headers from Long and Kitson.
But the home side gradually settled and went close when Rob Hulse flashed a shot wide and Kris Commons appeared to be pulled back when he turned away from Michael Duberry.
The big defender was close to putting the ball in his own net in the 38th minute, when he deflected a low cross from Commons just past a post with Marcus Hahnemann beaten.
Derby had finished the first half strongly, but Reading had a good chance to open the scoring at the start of the second when Long put Glenn Little in on the Derby left but his finish was wayward.
Gary Teale was on target when Derby went up the other end and Hahnemann almost let the ball spin out of his grasp and behind him but he was able to recover in time.
It was unlikely the game would finish goalless and Reading broke through in the 56th minute when Jimmy Kebe crossed from the left and this time there was no flag as Kitson headed in his second goal since his return to the club.
The visitors struck again in the 73rd minute when Jem Karacan opened up a square Derby backline and Long went clear to fire a shot under the advancing Stephen Bywater.
Derby responded well and almost pulled one back in the 76th minute when a Commons shot was cleared off the line by Duberry and the midfielder then forced Hahnemann to tip over a swerving shot from 25 yards.
But that was as close Derby came to finding a reply and they still need at least one point to be sure of playing in the Championship next season.