One day after matching the course record at Sherwood Country Club with a 9- under 63, Campbell only managed an even-par 72 on Friday. He stands at 9-under-par 135.
Fred Couples (68) and Kenny Perry (70) are knotted in fourth place at 5-under-par 139.
Tournament host and defending champion Tiger Woods continued to struggle on Friday. He shot his second consecutive even-par 72 and is 14th in the 16-man field.
'I just had a hard time finding my lines, a hard time seeing the putts,' said Woods, who also captured this title in 2001. 'I'm having a hard time feeling the slopes in my feet, in my hands, my body. I'm just having a hard time with it.'
Campbell was even on his round through his first six holes, but the man who collected his first major championship in June at Pinehurst looked poised for a huge lead.
He rolled in a 15-foot birdie putt at the seventh to move past Clarke into the lead at minus-10. Campbell parred the next two holes, but went on a birdie run that gave him a nice cushion.
At the par-4 10th, Campbell drained a 5-foot birdie putt to move three ahead of the field. He ran home a 10-footer for birdie at 11, then made it three in a row with a 10-footer at No. 13. Campbell was now five clear of his closest competitors, but Sherwood toughened up later in the round.
The par-3 15th proved to be the first challenge for Campbell. His tee ball flew over the green and the New Zealander chipped 12 feet past the hole. Campbell's par putt never touched the hole and he converted a 3-footer for bogey.
Campbell struggled at the next par-3, the 17th. His 8-iron moved well right of the flag, but Campbell nearly holed the improbable birdie try. Campbell missed another 3-footer and was forced to make a bogey putt that was longer than his par effort.
The worst was yet to come for Campbell. An errant drive and a poor approach that landed in the hazard at the finishing hole led to a double bogey.
Luckily, none of his challengers played any better over the closing holes so Campbell still takes a fairly healthy lead into the weekend.
'I hit some quality shots and some crap and some average shots,' acknowledged Campbell. 'I had it going quite nicely after 12 holes, I was 4 under, and then the wheels came off. And the wheels came off very, very quickly.'
Campbell, who was named European Tour Golfer of the Year last week, had quite a different round on Friday compared to his record-tying day on Thursday. The U.S. Open champion struggled with the putter in round two, but took some solace in his play.
'I'm going to stand on the tee tomorrow three shots ahead, I've actually increased my lead by one shot,' said Campbell. 'You just go out there and play, and your mind just keeps on ticking along, and all of a sudden you get a wake up call and you start panicking.'
Chris DiMarco, Luke Donald and David Howell all posted rounds of 4-under-par 68 and are tied for sixth place at minus-4. Thomas Bjorn (71), Tim Clark (70) and Jim Furyk (68) share ninth at minus-3.
Davis Love III, a two-time winner of this event, fired a 5-under 67 on Friday and is knotted in 12th place with David Toms, who shot a 70 in round two. The pair are tied at 1-under-par 143.
Woods is next at even-par 144, followed by Fred Funk (73) at plus-1, and Colin Montgomerie (70) at 2-over-par 146.