Two second half goals from Kevin Stewart and one from Kamil Grosicki resulted in an afternoon to forget for the Town.
Luton started the better of the sides and were on the front foot from the first whistle, but the game eluded their reach as Hull were ruthless towards the end of the contest.
The Hatters began in good fashion as James Bree had the ball on the left hand side and spotted Izzy Brown bursting through the middle. The midfielder unselfishly passed the ball wide to Harry Cornick - who was free in space - but his effort was blocked behind for a corner.
Minutes later Hull warned the Hatters of their threat going forward as Grosicki went close in the 12th minute.
Jackson Irvine won possession in midfield and played the ball through for Grosicki to run on to, but as he tried to square the ball across goal, Luton nullified the threat and cleared.
Before the half-hour mark, Irvine spurned the best opportunity of the half as he headed over Eric Lichaj’s cross after good play from the Tigers.
Tom Eaves produced the game’s first shot on target just a minute before half-time, but his tame effort was gathered with ease by Simon Sluga.
Hull City took the lead in the 64th minute as Stewart fired the ball into the top left corner as the ball broke to him from 12 yards out.
The away fans thought they had a second just four minutes later but Grosicki’s shot from distance rippled the side netting.
The Town’s first notable chance of the afternoon came in the 71st minute when Ryan Tunnicliffe’s effort was narrowly deflected wide after brilliant individual play from substitute George Moncur.
From the resulting corner, James Bree had a header saved and James Collins hit the post, before George Long gathered the ball and put an end to the attack.
Luton threatened in the latter stages as Andrew Shinnie’s free-kick was headed over by Dan Potts inside the six-yard box. That proved to be costly though as the Tigers went up the other end and got their second.
The ever dangerous Grosicki was the man who got it, after darting in from the left-hand-side and firing past Sluga into the bottom corner.
In the 90th minute, the away side got a third after a defensive mix-up. Jarrod Bowen ran through on goal and his effort squirmed under Sluga and in trying to clear, Potts hit the ball against the keeper and left Stewart to force it home.
The 40th meeting between the two sides was without doubt one to forget, as the Hatters now divert their attention to Leicester City in the Carabao Cup on Tuesday night.
TOWN: Sluga, Bolton (Potts 76), Pearson, Bradley, Bree, Tunnicliffe, Shinnie, Brown (Mpanzu 65), LuaLua, (Moncur 65) Cornick, Collins. Subs not used: Lee, Jones, Butterfield, Shea (GK)
HULL: Long, Lichaj, De Wijs, Burke, Kingsley, Stewart, Irvine (Batty 84), Lopes (Honeyman 66), Bowen, Grosicki, Eaves (Magennis 45) . Subs not used: Tafazolli, Ingram, (GK), Bowler, Pennington
Yellows: Grosicki, Honeyman
Referee: Andy Madley
Attendance: 10,066 (1,033 away)