The Hatters moved level on points with seventh-placed Plymouth thanks to the win, while Pools remain just a point above the drop zone.
The hosts went ahead as early as the fifth minute when Jake Howells’ corner was headed in by Cameron McGeehan.
Luton then doubled their lead after 15 minutes as Shaun Whalley was felled in the area and Howells confidently beat Scott Flinders from the spot.
John Still’s side then had a number of chances to extend their lead with leading scorer Mark Cullen denied when one-on-one, Whalley’s side-footer being cleared off the line and Pools keeper Flinders making a superb reflex save from Elliot Lee.
Hatters stopper Elliot Justham produced a good reaction stop from Marlon Harewood’s deflected free-kick while in the second period, Jonathan Franks saw his effort go narrowly side.
Town then sewed up victory in the 71st minute when another corner was swung over and, after an almighty scramble, Scott Griffiths diverted the loose ball beyond Flinders.
Hatters could have added another in the final stages only for substitute Ryan Hall to blaze horribly over after a rapid counter-attack.