Wigan Athletic deservedly took the three points in front of Deepdale's biggest crowd of the season.
Latics strikers Nathan Ellington and Jason Roberts ran Preston ragged with the latter scoring after just 30 seconds following his £2million move from West Brom earlier in the week.
It was Preston's first home defeat since August and they got off to the worst possible start when Gary Teale's cross from the right was cheekily back-heeled home by Roberts.
John Filan made good saves from Tyrone Mears and Graham Alexander before Preston equalised on the half-hour when Dickson Etuhu headed Alexander's free-kick home.
On the stroke of half time, Wigan restored their lead when Nicky Eaden's inch-perfect cross was headed into the net by Ellington from seven yards out.
Preston brought on Michael Keane for Mears and George Koumantarakis for Brian O'Neil in the second half and Jonathan Gould made a good save from Lee McCulloch's header.
Ricardo Fuller had an effort ruled out for offside after 58 minutes but Wigan made it 3-1 in the 72nd minute when Ellington found Teale and the former Ayr United man hit a 15-yard shot into the top right-hand corner of the net.
Ellington made it 4-1 after 80 minutes when he turned Teale's cross past Gould.
Preston were awarded a penalty in the 86th minute when Jason Jarrett was adjudged to have fouled Richard Cresswell who was running down the left-hand side of the penalty area. Mr Leake pointed to the penalty spot and only Jason De Vos protested.
Alexander slotted the penalty home but it was mere consolation for a well-beaten Preston side.