Rob Hulse's goal and Kris Commons' penalty - either side of Luciano Becchio's equaliser - proved enough for the Rams to condemn Leeds to their first opening-day defeat in 21 years.
It was a miserable start to the Championship campaign for Simon Grayson's men, who despite plenty of energy in attack were indebted to goalkeeper Kasper Schmeichel for a string of outstanding saves to limit Derby to two goals.
County manager Nigel Clough, given a frosty welcome by the home fans because of his late father Brian's relationship with Leeds, will not be too worried about his side's finishing just yet, though, as they got their season off to a flying start.
Backed by a 27,000-strong crowd, Leeds started with bundles of energy but were given an early warning of Derby's attacking intent when Commons drove over after a weaving run.
Bradley Johnson then attempted to hook in from an improbable angle for Leeds as they sought out an opening, before they went close through Neill Collins' header from Neil Kilkenny's cross.
Elland Road fell into near silence shortly after, though, when former Leeds striker Hulse gave Derby a 13th-minute lead.
Hulse scored 20 goals for United during their last spell in the Championship, and refused to celebrate in front of his former fans when he drove home from an angle after Paul Green had robbed Jonny Howson of possession.
Howson scored one of the two goals that took Leeds up on the final day of last season, and he was soon making amends two minutes later, nipping in to intercept Robbie Savage's poor pass before squaring for the waiting Becchio to score.
The home side nearly went ahead after 23 minutes, with captain Richard Naylor volleying against the bar, before falling behind again four minutes later.
Tomasz Cywka had too much pace for Lloyd Sam whose outstretched leg upended the winger, with Commons stroking home the resulting penalty.
Johnson should have equalised for a second time but headed Kilkenny's cross against the bar, while Derby could have made it three only for Green and Commons to be both superbly denied by Schmeichel.
Leeds started brightly after the interval, with Johnson's volley well saved by Stephen Bywater, before Schmeichel denied Green with a brave save with the midfielder just a couple of yards out.
Bywater recovered quickly to keep out a Kilkenny strike that had initially taken him by surprise shortly after the hour, before Schmeichel took centre stage again with a tremendous double save.
The Dane, a summer signing from Notts County, fell to his left to keep out Hulse's drive, before springing up to block Shaun Barker's follow-up effort.
Collins then had a header cleared off the line by Gareth Roberts as Leeds maintained their search for a leveller, but it was to no avail.