Two goals from Nathan Ellington and one each from his strike partner Jason Roberts and midfielders Alan Mahon and Lee McCulloch brought Wigan their first home victory over their Lancashire rivals since 1992.
The final scoreline bore little resemblance to a scrappy first half that saw McCulloch's header edge the home side in front, but the turning point came just before the break when North End centre-back Chris Lucketti had what seemed a perfectly good goal disallowed.
Wigan never looked back and their second-half display served notice that they are the team to beat in the race for the Premiership.
Wigan: Filan, Eaden, Breckin, Jackson, Baines, Teale, Bullard (Wright 76), Mahon (Flynn 82), McCulloch, Roberts, Ellington (Graham 84). Subs not used: Walsh, McMillan.
Booked: Bullard.
Goals: McCulloch 27, Mahon 52, Ellington 57, 72, Roberts 79 pen.
Preston: Gould, Mawene (Lewis 60), Lucketti, Davis, Alexander, Sedgwick, O'Neil, Etuhu, Broomes, Cresswell, Agyemang. Subs not used: Ward, Davidson, Daley, Lynch.
Booked: Broomes, O'Neil.
Att: 10,565
Ref: M Atkinson (W Yorkshire).