Lions defender Darren Purse headed the hosts in front in the 42nd minute from a James Henry corner and Josh McQuoid added a second two minutes later.
McQuoid took a pass from John Marquis and fired into the top left corner with a superb right-footed strike from 30 yards.
North End's 22nd defeat of the season was confirmed after the break as Marquis added a third, shooting low into the net from six yards.
Henry's penalty sealed the rout in the 65th minute. North End goalkeeper Iain Turner felled McQuoid and Henry stepped up to fire home from the spot into the top right corner.
The result lifted Millwall to within two points of sixth-placed Nottingham Forest and left Preston five points from safety with only three games remaining.
Source: PA
Source: PA