Statistics of 19-9 efforts at goal and 56 per cent possession in our favour counted for little as well-taken goals from Luke Varney and Ross McCormack won it for the home side.
Both goals came out of the blue. Varney raced clear from Michael Brown's ball over the top in the 15th minute and just when we were looking to try to impose ourselves at the start of the second half, McCormack latched onto Diouf's pass and hit the top corner.
Clint Dempsey gave us hope with a fine glancing header from Gareth Bale's cross on 58 minutes but with the likes of Brown, Rodoplh Austin and Diouf snapping away at our heels, we couldn't settle into a pattern and there were few sights at goal after that.
The best chance arrived in the final minute as substitute Jon Obika raced onto Benoit Assou-Ekotto's pass but the ball wouldn't settle down for him and a combination of Jamie Ashdown and Lee Peltier kept him out.
Andre Villas-Boas made five changes to the team that drew against United last weekend.
Brad Friedel was back in goal and there were returns for Jan Vertonghen, Assou-Ekotto, Tom Huddlestone and Gylfi Sigurdsson.
We had the better of the first half but couldn't convert one of our 12 efforts at goal.
Sigurdsson glanced a header straight at goalkeeper Ashdown after seven minutes and the goalkeeper produced fine saves to deny Huddlestone and Dempsey from distance and then Bale from a tight angle after the winger turned Peltier and Aidan White inside-out down the right.
At the other end, Leeds opened the scoring after 15 minutes when Brown hooked a pass forward from just inside his own half, Diouf missed his attempted flick on and that appeared to catch us out as we stood square, Varney raced through unchallenged to calmly slot past Friedel.
We dominated play after the goal - Ashdown's low tip away at full stretch to deny Huddlestone from 20 yards on 29 minutes the pick of the home keeper's saves - and we got into a number of dangerous positions without reward.
However, there was a warning just before the break as Diouf flicked into the path of McCormack, but Friedel was off his line in a flash to block.
We needed a positive start to the second half but it was Leeds who struck in the 50th minute. Diouf lobbed the ball between defenders into McCormack's path and the front man drove into the box, switched onto his left foot and fizzed his shot past Friedel.
The response was instant. Dempsey slid Lennon's cross wide and was there again in the 58th minute to glance his header from Bale's centre beyond Ashdown and into the top corner.
Moments after the goal, Obika and Mousa Dembele entered the fray for Sigurdsson and Huddlestone as we switched to a 4-4-2 system.
Clear-cut chances remained at a premium though as Leeds continued to break up play. Indeed, the next sight of goal fell the home team's way as Friedel saved well from McCormack on 72 minutes.
Dempsey hit a goalbound shot that was blocked by Peltier a minute later but we had to wait until the 90th minute for our next, and final, chance as Obika's moment of glory was snubbed out by Peltier and Ashdown.
Leeds United (4-4-1-1): Ashdown; Byram, Lees, Peltier, White; Green, Brown, Austin, Varney; Diouf (Pearce, 90); McCormack (Somma, 90+2). Unused subs: Kenny, Tonge, Norris, Hall, Dawson.
Spurs (4-2-3-1): Friedel; Naughton (Walker, 66), Caulker, Vertonghen, Assou-Ekotto; Huddlestone (Dembele, 58), Parker; Lennon, Sigurdsson (Obika, 58), Bale; Dempsey. Unused subs: Gomes, Dawson, Livermore, Townsend.
Yellow cards: Leeds - Diouf, Brown. Spurs - Vertonghen, Assou-Ekotto.
Goals: Leeds United - Varney (15), McCormack (50). Spurs - Dempsey (58).
Referee: Mr K Friend.