Two great first-half goals by midfielder Richard Chaplow continued the Lilywhites' impressive midweek run which now stretches back to February 2001.
Preston opened the scoring after 22 minutes when captain Paul McKenna had a free-kick which Youl Mawene headed down and on the line Chaplow scored from close range.
Stoke's Rory Delap had several dangerous long throw-ins and Liam Lawrence hit an out-swinging corner from which Ryan Shawcross rattled the outside of the right-hand post from ten yards.
Ricardo Fuller shot wide of the left-hand post and Chaplow crossed for Simon Whaley to head wide of the same upright.
Shawcross fouled Karl Hawley 20 yards out and McKenna took a short free-kick and Chaplow hit an unstoppable 20-yard shot into the bottom corner to make it 2-0 to Preston after 33 minutes.
Stoke's former Preston man Danny Pugh was booked for a foul on Whaley and Chris Sedgwick received a yellow card for a foul on ex-Preston striker Fuller.
It was Fuller who brought a great save from Andy Lonergan after 55 minutes when he hit a close-range right foot shot at the keeper.
Shawcross was booked for a foul on Callum Davidson and Leon Cort went down awkwardly and had to be stretchered off in the 70th minute.
Lawrence was booked for a foul on Preston substitute Darren Carter and Glenn Whelan barged Mawene and was also booked.
With a minute to go, Fuller had another shot saved by Lonergan for a corner and the fourth official signalled seven extra minutes, but it finished 2-0 to Preston.