Luton posted their first away win since October and heaped more pressure on Port Vale manager Dean Glover.
Vale took the lead against the run of play when John McCombe prodded home Adnan Ahmed's 25th-minute free-kick.
Luton equalised before half-time when Ian Henderson set up Asa Hall to fire in his eighth goal of the campaign.
Kevin Gallen slotted in after half-time and Chris Martin sealed it when he beat Anthony Griffith to a long pass and fired home Luton's third on 63 minutes.
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