The visitors were full value for their win, opening the scoring after six minutes with a goal by man of the match Jim Bentley, who latched onto a right wing cross from Craig Stanley to hit a 12-yard shot into the bottom corner of the net.
Neil Mellor had a diving header saved by Joe Lewis from a cross and Fraser McLachlan had a long range effort saved by Wayne Henderson.
Preston's first corner took 36 minutes to arrive and Kevin Nicholls hit an inswinger which the Morecambe keeper pushed wide for a corner.
There was a nasty challenge between Darren Carter and McLachlan just before the interval and the latter was stretchered off to be replaced by Jamie Burns.
Five minutes were added to the first half but Preston couldn't get back on level terms and Morecambe went in with a deserved 1-0 lead.
Sean St. Ledger was booked for a foul on Carl Baker in the 61st minute before Preston made a double substitution with Chris Sedgwick replacing Carter and Karl Hawley replacing Neil Mellor.
Brett Ormerod had a shot saved before Preston equalised with a Danny Pugh downward header into the corner of the net from a Hawley cross.
Morecambe were not to be denied their moment of glory however and David Artell deservedly won them the game with five minutes remaining when Preston keeper Wayne Henderson dropped a free-kick, leaving Artell with an easy tap in.