Goals from Sam Gallagher, John Buckley and Darragh Lenihan in an exciting first half had put them in control.
Before a goal in the second from Lewis Travis wrapped up those crucial three points as they aim to get out of the EFL Championship.
Story of the match
And Rovers kept the pressure up from there, doubling their lead just four minutes later, with Buckley brilliantly picking out the bottom corner from 25 yards.
Tony Mowbray's side certainly shrugged off the idea of a late season collapse as they threatened to overwhelm Preston. But the Lilywhites held firm and found themselves a foothold.
However that's as close as they came to a revival, as Lenihan met a free-kick with his head at the back post to restore the away sides two-goal advantage just before the break.
North End began the second period in more encouraging fashion, creating a couple half-chances, but just seven minutes into the half and the play-off chasers had killed the game off.
A superb through ball from Brereton Diaz found Travis who made no mistake with a low effort, scoring his first goal in two years for his sides fourth of the night.
However Blackburn continued to threaten for a fifth, as they looked to boost their goal difference. And came close to doing so when Brereton Diaz saw a header come off the crossbar.
A succession of substitutions and fouls meant that the final 15 minutes petered out with little incident, but Rovers will not have cared one bit, gaining that win they needed so badly.
Back-to-back bottom half finishes now looks likely for Preston
But he will no doubt be looking ahead for his chance to put his stamp on the squad when summer arrives, highlighted by games like this where they were simply rolled over by the better team.
A play-off push like that of their rivals is surely the aim, as supporters are unlikely to be happy with another mediocre season such as the last two.
Rovers fans can dream of promotion with play-off race going down to the wire
At the turn of the year, Blackburn were well within the automatic promotion hunt, sitting in the top two as recently as late January.
However a run of just two wins in 15 games and none in their last five had left them in ninth, and outsiders for a play-off spot.
But a big performance like this against their neighbours not only gives local bragging rights for Mowbray's men, it also moves them to within three points of sixth placed Sheffield United, keeping those hopes of the Premier League alive.
Man of the match
The Chilean international may not have gotten on the scoresheet, unluckily hitting the woodwork twice, but he definitely played his part.
Two assists and heavy involvement in another of the goals shows that he has so much more to his game than just finding the net himself.
Although 21 league goals is still something to be proud of from a player that may well find himself in the top flight next season, regardless of whether Rovers go up.