Rovers dominated from first minute to last and emphatically brushed aside a Preston North End side who played the second half with 10 men at Deepdale.
The turning point came just a minute before the interval when Joe Rafferty cynically dragged a rampaging Sam Gallagher down in the box when the striker was clean through on goal.
Rafferty saw red and Adam Armstrong stepped up to smash home the opener from the spot to sent Rovers into the break with the advantage.
Ben Brereton made it 2-0 early in the second half before PNE old boy Tyrhys Dolan came back to bite his former club with the third of the night when he tucked home Brereton's cross late into the second half to wrap up the points and earn the Lancashire bragging rights.
Tony Mowbray made three changes to his starting XI, with Ryan Nyambe, Lewis Holtby and Gallagher all returning to the team at Deepdale.
Suspension kept Bradley Johnson out of contention, whilst an injury ensured Joe Rankin-Costello was out of action. Elswhere, Gallagher, who scored a brace in the fixture in 2019-20, took the place of the benched Harvey Elliott.
The hosts' only alteration saw the return of Alan Browne from isolation, with the Republic of Ireland international coming in for Brad Potts in a like-for-like change from the team that started against Sheffield Wednesday three days earlier.
Rovers gained control of the game early on, and Ben Brereton went close to getting an early opener inside the opening 10 minutes, but dragged wide of Declan Rudd's right-hand post.
Another opportunity came Rovers' way soon after, but Darragh Lenihan's thunderous effort was beaten away by Rudd, with the ball reaching Armstrong who saw close range attempt blocked bravely by a couple of Preston bodies.
Armstrong was desperate to get back on the goal trail having failed to find the net at the weekend, and he unleashed a strike that flew over Rudd's crossbar just after the half hour mark.
Another Preston body denied Armstrong again with half time approaching, this time Patrick Bauer sliding in to stop the strike from an acute angle, before Brereton's delightful cross just needed a touch seconds later.
Drama arrived just seconds before the half time break, with Preston going a man down and Rovers going a goal up.
After a goalmouth scramble in their own box, Rovers worked the ball out intelligently, and Gallagher won his race with Rafferty and got across the home defender before being hauled down in the box.
Referee Tony Harrington had no choice but to brandish the red card for the left back, and up stepped Armstrong from the spot to slam into the bottom corner for his 13th goal of the season in all competitions to mark his 100th league start for the club in style.
A half time alteration for the hosts saw the anonymous Scott Sinclair replaced by Brad Potts. Potts moved onto the right side for PNE, with Tom Barkuizen dropping into the vacant left back spot.
It was Barkhuizen who went close to equalising for the home side just seven minutes into the second half, but he bent comfortably wide of Thomas Kaminski's left-hand post, before Rovers grabbed the second goal to add daylight to the scoreline.
Rothwell's quick footwork saw the playmaker zoom away from his man, thread a pass through to Brereton, and he made no mistake with a brilliantly tucked finish beyond Rudd and into the bottom right-hand corner.
The goal knocked the stuffing out of Alex Neil's side, with Rovers bossing possession and continuing to work the chances.
It was the excellent Gallagher who was next to try his luck, but the big man swung a shot right of Rudd's goal with just 22 minutes of the clash remaining.
But the next opportunity saw Rudd beaten once more, with Dolan returning to haunt his old employers by tapping home Brereton's low ball in to add gloss to the scoreline with his third goal of the season.
The visitors were still going for the jugular and substitutes John Buckley and Jacob Davenport both saw strikes fly past the post inside the final 10 minutes as Mowbray's men went in search of more goals.
Gallagher looked to have bagged the finish his play deserved when he turned home another superb ball in by the outstanding Barry Douglas, but the flag was up for offside and the scoreline and result remained 3-0 in what turned out to be the final action of the game.
The result moves Rovers up to 10th place in the table ahead of Saturday's home test against Barnsley at Ewood Park.
Rovers: Kaminski, Nyambe, Lenihan (c), Wharton, Douglas, Trybull (Davenport, 61) , Holtby (Downing, 69) , Rothwell (Elliott, 61 (Buckley, 80)), Brereton, Gallagher, Armstrong (Dolan, 69)
Unused substitutes: Pears, Chapman, Bell, Carter.
Goal: Armstrong pen, 45, Brereton, 53, Dolan, 76.
Booked: Trybull, 37.
Preston North End: Rudd, Fisher (Storey, 78), Bauer, Browne (c), Johnson (Stockley, 82), Rafferty, Ledson, Riis (Maguire, 78), Huntington, Barkhuizen, Sinclair (Potts, 46).
Unused substitutes: Ripley, Bayliss, Holland-Wilkinson, O'Reilly, Coulton.
Booked: Browne, 23.
Sent off: Rafferty, 44.
Referee: Tony Harrington.