Joe Garner and Jordan Hugill found the net to the delight of nearly 7,000 Lilywhites supporters who had made the short trip to East Lancashire for the lunchtime kick-off.
North End had fallen behind in the 13th minute to a shot from Rovers centre-half Elliott Ward, a player once on loan at PNE.
But the game swung their way 10 minutes later when home skipper Shane Duffy was red carded for handling a goalbound shot from Hugill on the line.
Garner drilled home the resulting penalty for his sixth goal of the season - two of which have now come against his former club.
Then two minutes before half-time, Hugill volleyed home superbly at the back post after being found by a lovely ball from Paul Gallagher.
North End had chances to stretch their lead on the break in the second half, with Ben Pearson, Daniel Johnson and Jermaine Beckford all having sights of goal.
But the two first-half goals proved enough to give them a third derby away win of the campaign after victories at Burnley in December and Bolton last month.
Garner and Alan Browne had returned to the starting XI after suspension and injury respectively, with Callum Robinson and Johnson dropping down to the bench.
Garner came in to partner Hugill up front, with Browne in a three-man midfield with Gallagher and Pearson.
North End lined-up 3-5-2, with Tom Clarke, Bailey Wright and Greg Cunningham the three at the back.
The first-half was full of action from the start, a fourth-minute goalbound shot from Tony Watt blocked by Clarke.
Watt pulled a groin muscle when taking the shot and had to be replaced by Simeon Jackson.
Hugill had PNE's first chance, his shot from the edge of the box blocked by a Rovers boot before it got near the keeper.
Rovers took a 13th minute lead, Elliott Bennett's corner from the left met by Hope Akpan in the air.
His header was tipped against the bar by Anders Lindegaard, the ball coming straight out to Ward who picked his spot with a first-time shot from 10 yards.
With their tails up, Rovers threatened again with another Bennett corner finding Ben Marshall on the edge of the box, his shot well blocked by Wright.
The game swung Preston's way in the 23rd minute, Browne's shot from the edge of the box pushed out by keeper Jason Steele into the path of Hugill.
His follow-up shot was destined for the bottom corner until centre-back Duffy dived full length on the line to push it away with his hand.
Referee Eddie Ilderton pointed to the spot after being consulted by his assistant on the far side and then pulled out the red card to send Duffy for an early bath.
Garner stepped up to slam the penalty low into the net and certainly didn't hold back with the celebrations against his former club.
Rovers responded to Duffy's dismissal by substituting Jackson who had earlier replaced Watt and bringing on Matt Kilgallon.
North End went in front two minutes before the interval, Gallagher and Hugill combining with lethal effect.
When Garner was crowded out on the edge of the box as he tried to get a shot away, the ball fell into the path of Gallagher.
He lifted a delightful chipped cross over to the far post which Hugill met beautifully with a right-foot shot which beat Steele all ends up.
At the start of the second half, Akpan tested Lindegaard with a curling shot from 25 yards, one which the Danish keeper dived to hold.
PNE missed a golden chance to stretch their advantage in the 54th minute, Reach getting down the left channel and pulling the ball back into the middle for Pearson.
Unfortunately, the midfielder steered his first-time shot inches wide of the post.
Pearson was later involved in a clash with Bennett and Ward, which resulted in him and Ward both being booked.
With that hanging over him, Pearson was substituted in the 63rd minute and replaced by Johnson.
North End were content to play on the break as the second half went on, stretching the play wide to make the pitch big against the hosts' 10 men.
Cunningham tried his luck with a low shot from distance, Steele getting behind it to gather at the second attempt.
Former Preston striker Chris Brown, on as sub for Akpan, was booked for going to ground under a challenge from Wright.
Soon after, he got on the end of a Bennett free-kick and saw his header saved comfortably by Lindegaard.
Paul Huntington replaced Reach in the 80th minute, Cunningham moving forward to Reach's wing-back role as North End stayed in their 3-5-2 shape.
Just after the change, Calum Woods got away down the right of the box and pulled the ball back to find Johnson.
The substitute got a shot away but Ward's out-stretched foot took it away from goal.
Four minutes from time, Beckford joined the action in place of Garner and almost found the net within sixty seconds of coming on.
Gallagher's long ball sailed over the Rovers back line to release Beckford down the left channel.
He cut into the box and hit a low shot which flashed inches past the far post and wide.
North End saw out four minutes of stoppage-time without too many problems, the final whistle greeted by a huge roar from the away end.
Blackburn: Steele, Marshall, Duffy, Ward, Spurr, Bennett, Lenihan, Akpan, Gomez, Watt (Jackson 7, Kilgallon27), Graham. Subs (not used): Henley, Brown, Grimes, Conway, Raya.
PNE: Lindegaard, Clarke, Wright, Cunningham, Woods, Pearson (Johnson 63), Gallagher, Browne, Reach (Huntington 80), Garner (Beckford 86), Hugill. Subs (not used): Vermijl, Robinson, Doyle, Kirkland.
Referee: Eddie Ilderton (Tyne and Wear)
Attendance: 21,029 (6,984 PNE)