Gary McSheffrey's first hat-trick for Birmingham ensured Steve Bruce can celebrate his fifth anniversary at St Andrews on top of the Championship.
Despite struggling early on, the Blues were two up by half time, McSheffrey slotting in Cameron Jerome's cut-back and then drilling in from 18 yards.
Brett Ormerod poked in to give Preston hope but North End were left to rue a host of missed chances late on.
McSheffrey wrapped it up from the spot after being fouled by Sean St Ledger.
"Gary McSheffrey has been a fantastic acquisition for us. There were times in the summer when it looked like the move from Coventry was not going to happen.
"I kept pushing and pushing. Gary was my number one target. He is everything I admire in a player.
"He is full of life and guts and determination and he is a very good finisher."
"Everyone would admit the finishing was the difference, we played as well as we have for a long time.
"We created plenty of chances but if you don't finish them you're going to be punished, we had one of those days.
"On this occasion we were excellent but we have been punished by a quality team in Birmingham."
Birmingham: Maik Taylor, Kelly, Jaidi, Upson, Sadler, Larsson, Muamba, Clemence, McSheffrey (Campbell 90), Bendtner, Jerome (Nafti 86).
Subs Not Used: Doyle, Martin Taylor, Danns.
Booked: Jerome, Muamba, Nafti.
Goals: McSheffrey 32, 40, 89 pen. Preston: Nash, Alexander, St. Ledger, Chilvers, Hill, Whaley, McKenna, Sedgwick, Pugh, Nugent (Dichio 81), Ormerod.
Subs Not Used: Lonergan, Miller, Lewis Neal, Wilson.
Booked: St. Ledger, Sedgwick, Pugh.
Goals: Ormerod 45.
Att: 23,159
Ref: M Riley (W Yorkshire).