Neil Warnock made two enforced changes due to injury, Luke Varney coming in for Adam Drury and El-Hadji Diouf replacing Ross McCormack.
And it was Diouf who threatened first when he won an early corner as United mounted the first real attack of the game.
Moments later, Diouf was the main man again when he won a penalty after being clipped by Hull defender James Dudgeon on the edge of the box. Luciano Becchio stepped up to take the spot-kick and he coolly converted.
It gave United the early advantage and, clearly a real boost, with Rodolph Austin having a shot blocked on the line and Diouf being denied by Ben Amos.
The game marked an Elland Road return for Alex Bruce and he was booked inside 20 minutes for excessive protesting. The former United man had made his feelings clear after the penalty decision and clashed with the referee again after a Sam Byram challenge on Abdoulaye Faye.
But Hull were level on 23 minutes when the ball broke kindly to Ahmed Elmohamady after a mix-up, and the Egyptian was handed an easy finish.
And the visitors were swiftly in front Faye found plenty of space to head a right wing cross beyond the reach of Paddy Kenny.
The first half continued to be a feisty affair, but there were no real chances for either side as Hull went in 2-1 to the good.
Austin tried his luck at the start of the second period, and his effort was followed by a worrying delay while Becchio received treatment after taking a knock on the ankle. The South American was swiftly replaced by Dominic Poleon.
The sub made a couple of early runs to lift the crowd and he also forced a good save from Amos after he cut in from the left.
But it was 3-1 to Hull on 76 minutes when Robert Koren finished off a sweeping move forward by tucking the ball Kenny.
The goal appeared to end the game as a contest, but United did rally briefly. Amos had to smother when under pressure and Poleon sent a shot wide after good work by Andy Gray.
And it was Gray who made his mark in the first minute of stoppage time when he headed home from a corner to reduce the deficit to set up a tense finale.
Lee Peltier did try his luck from distance and United looked to salvage something, but the clock ended any hopes of a comeback.