Steve McClaren's men came into the weekend three points clear of second-placed Bournemouth, but succumbed to two goals from Mirco Antenucci at Elland Road.
The Italian opened the scoring two minutes before the break, slotting past goalkeeper Lee Grant after the referee had played advantage following a Will Hughes handball.
Antenucci doubled the advantage with his seventh goal of the season five minutes into the second half - firing in from 10 yards after a Stephen Warnock cross to secure Leeds' first win over Derby in 13 attempts.
Derby's first defeat in four went unpunished, though, as Bournemouth threw away a victory that would have seen them top the table on goal difference.
Two goals in three minutes from Steve Cook and Brett Pitman put the hosts in control midway through the first half at Dean Court.
But, with a place at the summit in their sights, Bournemouth allowed Ed Upson to head level, before Alan Dunne nodded against the crossbar.
Millwall did pull level two minutes from time, though, when Magaye Gueye struck inside the box.
Middlesbrough also missed a chance to pull level on points with Derby - Rudy Gestede netting an equaliser for Blackburn Rovers deep into stoppage time after Patrick Bamford had opened the scoring in a 1-1 draw.
Ipswich Town now sit second after Noel Hunt - on loan from Leeds - came off the bench to score a debut goal in a 1-0 win at Charlton Athletic, while Brentford hammered Wolves 4-0 to go third and subject their visitors to a fourth defeat in succession.
Cardiff City won 1-0 at Watford to edge closer to the play-off positions, leapfrogging Nottingham Forest, who were beaten 2-1 at Birmingham City courtesy of a late Paul Caddis penalty, which came after Forest goalscorer Britt Assombalonga was sent off for illegally blocking a shot on the line.
At the other end of the table, Blackpool denied Rotherham United the chance to pull away from the relegation zone as they played out a 1-1 draw, while Wigan Athletic's first away match with Malky Mackay in charge ended in a 2-1 defeat at Sheffield Wednesday.
Brighton and Hove Albion slip into the bottom three following their 2-1 defeat at home to Fulham, although Darren Bent - on loan at the Amex Stadium from Aston Villa - did find the net against his former club.
The home side also saw Adrian Colunga sent off for two quickfire bookings in the closing stages.
Bolton Wanderers made it four games unbeaten with a 1-0 win over Huddersfield Town, and, at Carrow Road, Jake Cooper's brace saw Reading come from behind to beat Norwich City 2-1.
In tribute to the recent passing of international cricketer Phillip Hughes, Reading's Australian goalkeeper Adam Federici placed a cricket bat behind his goal to applause from opposition fans.
