Elijah Adebayo's 15th goal of the season set the Town on their way, before Harry Cornick rolled in his 11th and James Bree his first of the campaign, an absolute belter of a free-kick, to seal the points in the second half.
Manager Nathan Jones made one change to the side that beat Preston 4-0 in midweek, although Fred Onyedinma did come on in the early stages of that game following Reece Burke's injury, and he was selected to start in the right wing-back position.
Defender Tom Lockyer was named on the bench, as too was Pelly-Ruddock Mpanzu, who was forced off with a knock against Queens Park Rangers last Sunday.
Cameron Jerome was also an option as a substitute for Jones as the Hatters looked to head into the international break with a positive result at the MKM Stadium.
The Hatters' first chance arrived on six minute when Adebayo set strike partner Cornick free down the left, and he out-paced Sean McLoughlin and got his shot off from a tight angle, but Hull keeper Matt Ingram saved.
Moments later Dan Potts got down the same flank and crossed for Onyedinma, whose header was deflected behind for a corner, but the breakthrough wasn't long in coming.
The Tigers attempted to play the ball down their right from the full-back position, Amari'i Bell intercepted and the ball found its way to Adebayo who turned and drove towards the Hull area, eventually shooting from virtually the same spot as Cornick, only this time Ingram's foot could only deflect it inside the far post.
Hull tried to respond with a 25-yard free-kick that Keane Lewis-Potter hit over the bar, but it was Town who were dominating proceedings, and Luke Berry was next to have a go, teed up by Jordan Clark, but Ingram dived to his right to push the midfielder's shot around the post.
James Shea had to get his body behind Ryan Longman's fiercely-struck daisy cutter on 27 minutes, but the Hatters were soon pressing at the other end again, Potts carrying the ball out from the back and feeding Adebayo, who in turn set up Berry for another long-range shot that flew just over Ingram's bar.
Tom Eaves span and hit a half-volley that was too high with three minutes to go until half-time, but Kioso had handled the target man well to ensure the Hatters went in at the break with the advantage.
Hull came as close as they had to levelling three minutes after the restart when Alfie Jones met George Honeyman's free-kick with a flicked header, but the ball drifted safely wide of Shea's far post.
Lewis-Potter stung Shea's palms after cutting in from the left touchline on 51 minutes, then Jones made a double substitution, with injury forcing Kioso to be replaced by Lockyer, and Berry by Mpanzu.
Eaves couldn't generate any power behind a left-footed stab volley from captain Richard Smallwood's cross, and by the 56th minute the Hatters had doubled their lead.
Adebayo was the creator this time, pressing McLoughlin after the City centre-half dwelt on the ball when receiving it 30 yards from his goal from Ingram. The Town top scorer nicked possession, then had the presence of mind as Ingram came out to slip it to his left, where Cornick took a touch and steered it into an empty net.
Honeyman volleyed at the Town goal just after the hour, but it was comfortable for Shea to deal with and attention was soon switched to the other end.
Clark, once again magnificent in the Town midfield, drove at the City defence only to have his progress halted by a cynical trip by sub Tom Huddlestone. Bree stepped up to bend an absolute beauty, Beckham-esque, that bounced down off the underside of the Hull bar and over the line, with Ingram rooted to the spot.
Eaves reduced the deficit to two goals in added time at the end of the match but it wouldn't effect Luton's charge towards another big three points!
Goals:
Hull: Eaves (90+2)
Luton: Adebayo (9), Cornick (56), Bree (72)
