Wayne Rooney broke the deadlock on the stroke of half-time, but the home side struck back on the hour mark via a Craig Fagan penalty.
However, Sir Alex Ferguson's men made sure they finished the day second in the Premier League table after an own goal from Andy Dawson and a late strike from Dimitar Berbatov sealed their win.
Ryan Giggs came within inches of putting his side ahead early on. Kamil Zayatte was adjudged to have fouled Rooney on the edge of the Hull box which allowed the United skipper to step up and hit the ball just past Boaz Myhill's right-hand post with a curling free-kick.
Hull's best chance of the half fell to midfielder Seyi Olofinjana as Fagan found the Nigeria international in space with a pinpoint cross from the right.
However, the ex-Stoke man could only fire his effort straight at keeper Tomasz Kuszczak, who did well to parry the ball away.
Olofinjana then turned provider as he slipped a neat ball through to Stephen Hunt on the left but he placed his first-time left-footed effort just wide of the mark.
Moments later, Rafael Da Silva found himself unmarked in the box with time to pick his spot but his low right-footed effort was expertly saved by Myhill.
United did break the deadlock in first-half injury-time as the Hull defence failed to clear Darren Fletcher's cross from the right allowing Rooney to nip in and stab the ball home from close range.
Hull were back on level terms on 59 minutes when referee Alan Wiley awarded Hull a penalty after he judged Rafael to have pushed Jozy Altidore in the back.
Fagan stepped up to send Kuszczak the wrong way from the penalty spot to make it 1-1.
United restored their lead on 73 minutes as Rooney found the space down the right to slip a neat ball across the Hull goal which was met by a sliding Andy Dawson, who could only send the ball into the back of his own with Ji-Sung Park destined to convert at the back post.
The champions then went 3-1 up on 82 minutes as Rooney again slipped a clever ball across the Hull goal and this time into the path of Berbatov, who made no mistake from close range to register his fifth goal of the season.