Van Persie took sole possession of 10th place on the all-time list with Arsenal's second-minute opener and hit an almost identical goal for 2-1 in the 38th.
Alex Oxlade-Chamberlain scored his first league goal before relegation-threatened Blackburn was reduced to 10 men just before halftime when Gael Givet was sent off for a two-footed foul on Van Persie.
Mikel Arteta added a fourth goal, Oxlade-Chamberlain struck a fifth, Van Persie completed his hat trick with an unmarked finish in the 62nd and substitute Thierry Henry scored in injury time.
Van Persie now has 22 Premier League goals this season and 123 overall for Arsenal. Henry, who rounded off the rout with his second goal since returning to the London club on loan from Major League Soccer's New York Red Bulls, leads the standings with 228.
"When you feed him in the box, he is deadly," Arsenal manager Arsene Wenger said.
Arsenal's biggest margin of victory in the league since its 6-0 demolition of Blackpool in August 2010 boosted its chances of challenging for a top-four finish and dramatically improved its goal difference, which could prove crucial at the end of the season.
Fourth-place Chelsea, Newcastle and Liverpool are all still in contention for one of England's four Champions League qualifying spots.
Wenger lauded Oxlade-Chamberlain's contribution but said he was most pleased by the teamwork on display from his side.
"We were guided by the way we want to play football and not by any extra individualism," Wenger said.
The Gunners barely had to move out of second gear against Blackburn, which was in deep trouble even before Givet was given a straight red card. The central defender left the ground as he went into a challenge with both feet, leading with his studs to send Van Persie cartwheeling.
Givet apologized to Wenger as he trudged off the field and Blackburn manager Steve Kean said the defender also apologized to his teammates in the dressing room.
"I don't think the referee had a tough decision to make because we all know the rules now," Kean said. "If you leave the ground and go in with two feet, the challenge won't be accepted." But Arsenal was already 3-1 up, settling the nerves of a team that lost three and drew one of its last four league matches.
Teenaged right back Francis Coquelin started the move that led to the opener when he slipped a disguised pass with the outside of his right boot to Theo Walcott, who stayed onside and rolled in a cross for Van Persie to tap in from close range.
Morten Gamst Pedersen equalized in the 31st with a curling free kick into the top left corner but Van Persie restored Arsenal's lead. The move was almost identical to the one that yielded his opener, only this time Alex Song provided the pass forward to Walcott, who again provided the assist.
Oxlade-Chamberlain rounded goalkeeper Paul Robinson and finished for 3-1 in the 40th and, with Givet off the pitch, Blackburn disintegrated.
Arteta lashed in from the edge of the area for his first goal in two months and Walcott was allowed to make a mazy run across five defenders into the area, before passing to Oxlade-Chamberlain. Oxlade-Chamberlain took the ball inside the fullback with one touch and stuck it inside the post with his second.
Van Persie's rising finish from Coquelin's pass made it 6-1 and Henry, in space following an exchange of passes with Van Persie, completed the scoring with a low finish past Robinson.
"It's a horrible afternoon," Kean said. "They know they've let themselves down."
