Tigers end Town's Portman Road record
Blues fell to a first home defeat of the League One campaign as top of the table Hull claimed the three points in clinical fashion.
Sucker-punch goals from Mallik Wilks and Josh Magennis punctuated the first half, with subsitute Tom Eaves putting the result beyond any doubt midway through the second period.
Paul Lambert made four changes to the side who beat Shrewsbury at the weekend with Luke Woolfenden, Emyr Huws, Keanan Bennetts and James Norwood returning to the starting XI.
Hull took the lead inside the opening two minutes, Wilks firing into the bottom corner from the edge of the box.
Town looked to respond a few moments later after Norwood won a free-kick on the left wing however Brett McGavin's dangerous delivery was headed away from inside the six-yard box.
The visitors had Jacob Greaves to thank for maintaining their lead twice inside a minute, midway through the half.
First, he got in the way of Norwood's goalbound header from Luke Chambers' whipped cross before bravely denying Keanan Bennetts after the on-loan winger had nutmugged Callum Elder and sent a powerful shot towards the top corner.
Norwood was then put in behind by a lofted through ball from Woolfenden, the striker sending his shot from tight angle straight at Matt Ingram.
Blues were forced into a premature change with just over half an hour played, Freddie Sears unable to continue and being replaced by Jack Lankester.
Huws was the next to be denied for Town, his header from McGavin's corner being blocked before Hakeeb Adelakun ghosted into the box and sent a tame shot straight at Tomas Holy at the other end.
The visitors doubled their lead in first-half stoppage time just when Blues looked to be getting on top in the game, Magennis being left with a simple finish after bringing down Reece Burke's low cross into the box.
Magennis should have made it 3-0 just past the hour mark but he volleyed over the top from next to the penalty spot from Josh Emmanuel's cross.
Wilks could've added his second five minutes later, jumping over a tackle from Woolfenden before Holy got his body in the way of his right-footed strike when in one-on-one.
Norwood was once again denied from a tight angle by Ingram after played in behind by McGavin, with Kayden Jackson and Oli Hawkins entering the action shortly afterwards.
The visitors put the game to bed with just under 14 minutes remaining, Elder pinching possession on halfway before Eaves beat the offside trap and slotted past Holy from inside the box.
Blues kept huffing and puffing but to little avail as Hull's defence held firm.
Town: Holy, Chambers (C), Woolfenden, Nsiala, Ward, McGavin, Huws, Judge, Bennetts (Jackson 74), Norwood (Hawkins 74), Sears (Lankester 32).
Subs: Cornell, Nsiala, Kenlock, Drinan.
Hull: Ingram, Elder, Burke, Smallwood (C), Wilks (Coyle 82), Honeyman (Samuelsen 82), Emmanuel, Adelakun (Scott 62), Slater (Jones 63), Greaves, Magennis (Eaves 71).
Subs: Long, Batty.