Sir Alex Ferguson's side moved three points clear of Chelsea after Berbatov ended his goal drought to become only the fourth player to score five goals in a Premier League match.
Berbatov, who joined an elite club including Andy Cole, Alan Shearer and Jermain Defoe, opened the scoring after 75 seconds when he pounced on Wayne Rooney's flick.
Berbatov celebrates after scoring his fourth goal during the match between Manchester United and Blackburn Rovers. AFP |
It was Berbatov's first goal in 11 matches since his hat-trick against Liverpool in September and United didn't have to wait long to double their lead through South Korea midfielder Park Ji-Sung in the 23rd minute.
Berbatov put United further ahead four minutes later. The Bulgarian forward completed his hat-trick in the 47th minute, then Nani added the fifth a minute later.
Berbatov scored again in the 62nd minute and sealed a memorable performance with his fifth in the 70th minute.
Christopher Samba's late goal for Blackburn means Chelsea will regain top spot if they win at Newcastle on Sunday.
"When you are a striker people tend to only look at the goals you score," Berbatov said.
"For me, it is more about how I play, the assists I give, how I link with other players but today I scored so I am very pleased."
Arsenal briefly led the table after getting back on track at the end of a traumatic week with a 4-2 victory at Aston Villa.
The Gunners crashed 2-0 at Braga in the Champions League in midweek, just days after blowing a two-goal lead to lose 3-2 at home to north London rivals Tottenham.
But Andrey Arshavin opened the scoring in the 39th minute and Samir Nasri increased Arsenal's lead six minutes later.
Ciaran Clark's 52nd minute strike briefly gave Villa some hope before Morocco forward Marouane Chamakh poked in the third goal.
Clark scored again from close-range in the 70th minute but Jack Wilshere sealed the points with a diving header in stoppage time.
Gunners boss Arsene Wenger said: "It was a good mental response. This team is very interesting.
"They are all on the same wavelength and want to play the same football. They want to fight for each other too."
Manchester City's title challenge suffered a blow as Stoke's Matthew Etherington earned a 1-1 draw with a late equaliser.
City had taken the lead in the 81st minute through Micah Richards but Etherington levelled in stoppage time.
West Ham eased the pressure on boss Avram Grant and boosted their survival hopes with a 3-1 win over Wigan at Upton Park.
Reports claimed Grant was in danger of losing his job if the Hammers failed to win a fixture dubbed the "save our season match" by the club this week.
But Valon Behrami broke the deadlock with a cool finish in the 34th minute before Victor Obinna added the second in the 56th minute.
Rob Green saved a penalty from Wigan's Mauro Boselli, West Ham's Scott Parker struck in the 75th minute and Tom Cleverly's goal was no consolation for Wigan.
Sylvan Ebanks-Blake scored a last minute winner as struggling Wolves beat Sunderland 3-2 at Molineux.
Kevin Foley smashed in a fine strike for Wolves in the 50th minute, but Darren Bent levelled in the 67th minute.
On-loan Manchester United striker Welbeck put Sunderland ahead in the 77th minute. But Stephen Hunt levelled four minutes later and Ebanks-Blake bagged the decisive strike in the 89th minute.
West Bromwich Albion climbed away from the relegation zone with an impressive 4-1 win at Everton.
Paul Scharner put Albion ahead in the 16th minute before Chris Brunt curled home a stunning free-kick.
Tim Cahill reduced the deficit when he headed in his eighth goal of the season just before half-time.
Everton's comeback bid was ended when Mikel Arteta was sent off in the second half for a stamp on Gonzalo Jara.
Albion's Somen Tchoyi sealed the points for Albion, who added a fourth through Sylvain Distin's own goal and also had Youssouf Mulumbu sent off.
Bolton fought back from two goals down to earn a 2-2 draw against Blackpool at the Reebok Stadium.
Ian Evatt and Luke Varney put Blackpool in control. But Martin Petrov's goal sparked a recovery capped by a Mark Davies equaliser in the 89th minute.
Clint Dempsey earned Fulham a 1-1 draw with Birmingham, who took the lead through Sebastian Larsson.
What the stars mean:
★ Poor ★ ★ Promising ★★★ Good ★★★★ Very good ★★★★★ Exceptional