Preston made it six home wins in a row and deservedly ran out easy winners.
David Nugent hit a 17-yard shot over the bar from a Danny Dichio pass after 15 minutes and former Leeds full-back Danny Pugh hit a left-foot free-kick, also over the bar.
Dichio made it 1-0 to Preston after 19 minutes with his fourth goal in three home games.
Nugent pulled the ball back from the left wing and Dichio headed into the top corner from 8-yards.
Pugh made it 2-0 after 22 minutes when Nugent again pulled the ball back from the right and crossed for defender who fired home into the bottom right-hand corner of the net.
Nugent shot over from 20-yards and Paul McKenna shot wide of the right-hand post from 30-yards.
Ian Moore was booked for a foul on Matt Hill and Sean St. Ledger had a header saved right on half-time.
Nugent made it 3-0 just after the restart from a great cross by Simon Whaley from the right.
Wise made a double substitution bringing on Robbie Blake and Geoff Horsfield for Adam Johnson and Moore.
Shaun Derry forced a save from Carlo Nash before Richard Cresswell was booked for a foul on Whaley.
Then David Healy was booked for a foul on Hill and it was Healy who pulled a goal back for Leeds with 11 minutes to go when he hit a left-foot volley from a Cresswell cross.
Lewis Neal, who had come on as substitute for Pugh, made it 4-1 to Preston with seven minutes to go with a 25-yard shot which got a slight deflection.