Ernie Els, who held the first-round lead, shook off some early bogeys with a strong finish at the Wentworth Club for a round of 71. He was joined by Darren Clarke, Phillip Price and Joakim Haeggman at 9-under-par 135.
Rose has had little success in his three previous appearances at this event with a missed cut and no finish better than 32nd, but the young Englishman, who held the 36-hole lead at the Masters, made his way around the West Course with a barrage of birdies to move into the outright lead.
Rose hit a 9-iron off the tee at the second to 15 feet for the first of three consecutive birdies before running into trouble with a bogey at the fifth. At the par-4 eighth, Rose played his second shot inside 12 feet and drained the birdie putt to reach 8 under.
He added a birdie at the par-5 12th and ran home a 25-footer for a birdie at the par-4 16th.
Rose, who rarely found the fairway off the tee on Friday, missed the short grass again at the par-5 17th and left his second shot in the rough as well.
The 23-year-old missed the green with his third, but chipped in for a birdie the hard way to move to minus-11.
'You can never get ahead of yourself, really,' said Rose. 'Like you sort of churn away a little bit when you should be relaxing. It's not worth thinking about tomorrow till tomorrow comes.'
Rose, a two-time winner on the European Tour, has yet to return to the winner's circle since his last title at the 2002 British Masters.
'It's been a while, for sure,' said Rose. 'I've had a lot of good performances in between without winning, which has obviously kept me feeling relatively upbeat. But there's nothing better than actually holding up a trophy, that's for sure.'
Els, who lives at Wentworth, posted a 64 on Thursday, but had some trouble early on in the second round to find himself clawing his way back up the leaderboard.
'It was a bit of a difficult day,' said Els. 'I actually struck the ball well the first couple of holes, but I had no feeling with the putter.'
The South African stumbled to a bogey at the third and dropped another shot at the par-4 eighth. Els recovered on the back side and converted a 15-foot putt for a birdie at the par-5 12th.
Els then birdied each of the last two holes to finish two shots back in a tie for second.
'It could have been a really tough day, but I just tried to hang in there,' said Els. 'I obviously wasn't playing as good as I played yesterday. But I think nobody really played well this afternoon, so I don't think I lost too much ground, although I lost the lead.'
Clarke got off to a quick start with a birdie at the second and added an eagle at the par-5 fourth to jump to 7 under. The Ulsterman cooled down from that point on however, but managed a pair of birdies on the inward half en route to a round of 67.
'It was pretty good early on and then let a few slip toward the end,' said Clarke. 'Wasted a few. Disappointed to let a few go.'
Ian Poulter carded a 68 to join Angel Cabrera, Anders Hansen, Stephen Dodd and Marcel Siem in a tie for sixth place at 8-under-par 136.
Vijay Singh managed a 73 to finish in a group at 5-under-par 139 that featured Miguel Angel Jimenez and Nick Faldo.
Defending champion Ignacio Garrido struggled to a round of 76 to finish 10 shots off the pace at 1-under-par 143.
The 36-hole cut fell at even-par 144 with such names as Lee Westwood and reigning British Open champion Ben Curtis falling short of the mark.