North End boss Graham Westley made four changes to the side that lost to Crawley at the weekend and they responded with an emphatic victory in Tuesday night's League One encounter.
Westley's men have now won three of their last four league games, while Neale Cooper's Hartlepool remain without an away win since March.
Joel Byrom's opener, his first for the club, owed much to a momentary lapse in concentration from Peter Hartley, who needlessly conceded a corner with a misdirected pass-back.
Preston did not relent from that set piece until Byrom thrashed his first goal for the club into the top corner before Stuart Beavon doubled the lead little more than a minute later, curling a sumptuous effort into the top corner from outside the box.
Substitute Jack King headed a third from Beavon's excellent cross midway through the second half, and left back Laird then scored a rare double in the last seven minutes to complete the rout.