A first league goal for Jozy Altidore saw the Tigers 1-0 up at half time, then a stunning strike from George Boateng doubled the home side's lead early in the second half.
The visitors made it a tense last half an hour however, as a goal from Emmanuel Adebayor on the hour mark put the Blues firmly back into the game.
Hull City 2-1 Manchester City: As it happened
Jan Vennegoor of Hesselink was presented with a chance on the 20-minute mark as a neat header from Steven Mouyokolo found the Hull forward with space inside the box, but the Dutchman dragged his left-footed volley wide of the post from 12 yards.
Boateng was next to come close for Hull as he found himself in space just outside the box, but the ex-Middelsbrough man's left footed strike flew high and over the visitors' crossbar.
Phil Brown's men then deservedly broke the deadlock on 31 minutes as neat play between Boateng and Vennegoor of Hesselink provided Altidore with a chance on the edge of the box.
The USA international made no mistake as he slotted the ball into the bottom corner of the net with a first-time, right-footed effort to register his first Premier league goal for the Tigers.
Wayne Bridge came close for the visitors in first-half injury time, but his left-foot shot from a narrow angle was well palmed away by keeper Boaz Myhill.
Hull found themselves 2-0 up nine minutes into the second half as a Stephen Hunt corner was headed out by Kolo Toure, but only as far as Boateng who fired a blistering half-volley into the top right corner of the net, leaving keeper Shay Given with no chance, to register his first goal of the season.
City grabbed one back minutes later as Hull failed to clear their lines following an Adam Johnson corner, resulting in a huge goalmouth scramble, in which Adebayor found space to slam a first-time effort into the roof of the net, claiming his seventh goal of the campaign.
Roberto Mancini's men had a great chance to level in the dying minutes as Gareth Barry found Carlos Tevez free inside the box with pin-point cross, but the Argentina international could only send the ball straight into the body of Myhill.