Derby manager Billy Davies masterminded a victory over his old club at Deepdale which lifts the Rams to second in the Coca-Cola Championship table.
Steve Howard scored twice in the space of three minutes to give Derby maximum points which sees them leapfrog Paul Simpson's side and close the gap on table-topping Birmingham to three points.
Derby flew out of the blocks in the second half and took a deserved lead through Howard in the 48th minute.
A break down the right by David Jones culminated in a rasping right-footed shot by Morten Bisgaard from the right side of the penalty area from 12 yards.
Preston goalkeeper Carlo Nash made a hash of the save to his near post and parried the ball to Howard who tapped the ball into the net from six yards.
Derby were two goals to the good only three minutes later after Preston defender Liam Chilvers brought down Jonathan Stead in the penalty area and the referee pointed to the spot.
Nash correctly guessed the direction of Howard's effort but his firmly-struck kick nestled into the bottom right of net.
Preston introduced Paul McKenna in the 62nd minute and the midfielder began to give the home side a foothold in the game.
McKenna had a decent shot from 20 yards in the 74th minute which whistled past the post and then forced Stephen Bywater to make a save with a right-footed drive from 18 yards three minutes later.
Preston's spell of pressure eventually paid off and they pulled a goal back through top scorer David Nugent in the 79th minute.
Graham Alexander crossed from the right wing and Derby defender Mohammed Camara slipped to allow Nugent to toe-poke the ball past Bywater into the bottom right of the net from 12 yards.
Earlier in the first half Preston's Brett Ormerod and Derby's Michael Johnson were guilty of missing clear-cut chances.
Derby's best opportunity of the half to open the scoring came in the 22nd minute after Matthew Hill fouled Bisgaard.
Jones delivered a dangerous ball from the resulting free-kick which was fumbled by Nash.
Johnson almost cashed in on Nash's fumble but could only direct his header on to the bar from inside six yard box and Sean St Ledger cleared.
Simpson's side found themselves with a good chance to break the deadlock seven minutes later through Ormerod.
Nugent stole in front of Johnson and fed the ball to fellow forward Ormerod who only had the goalkeeper to beat. Ormerod saw his shot from the edge of the penalty area tipped over the bar by Bywater.
Derby almost trebled their advantage in the 84th minute when Stead broke free but he smashed the ball over the bar from the edge of the box.
Five minutes of added time gave Preston hope as they pushed for an equaliser but it was Derby who almost scored in the dying stages as Nash blocked from substitute Arturo Lupoli in a one-on-one situation.
Preston forced a late corner which was curled in by Danny Pugh but Bywater punched the ball clear and Derby held on to take the points.
Teams:
Preston Nash, Alexander, St. Ledger, Chilvers, Hill,Sedgwick (Whaley 61), Miller (Lewis Neal 75),Davidson (McKenna 62), Pugh, Nugent, Ormerod.
Subs Not Used: Lonergan, Wilson.
Booked: Davidson, Ormerod.
Goals: Nugent 79.
Derby Bywater, Edworthy, Leacock, Michael Johnson, Camara,Jones, Bisgaard (Lupoli 69), Barnes (Malcolm 84), Oakley,Howard, Stead (Moore 88).
Subs Not Used: Grant, Seth Johnson.
Booked: Howard, Leacock, Oakley, Stead, Jones.
Goals: Howard 48, 51 pen.
Att: 19,204
Ref: L Probert (Gloucestershire).