The visitors – who climbed to second with the win – started brightly with Mellor poking home his first from close range after seven minutes before unselfishly feeding Iain Hume two minutes later to tuck the ball under Nikki Bull from 10 yards.
Wycombe responded almost immediately and former Preston star Gareth Ainsworth swept the ball home from two yards in the 12th minute after a fumble from Andreas Arestidou.
Incredibly the Chairboys were level two minutes later when Conor McLaughlin bundled over Kadeem Harris and Scott Donnelly coolly dispatched the penalty.
The turnaround was complete in the 27th minute when Donnelly’s inswinging corner was headed home at the near post by Stuart Beavon to give Wycombe the lead.
Hume raced clear of the Wycombe defence and delicately chipped over the advancing Bull for his second to level for Preston after 64 minutes, before Mellor smashed into the roof of the net for his seventh league goal of season 17 minutes from time.