Ben Curtis, playing in the final group with Rose, posted a 3-under 67. His bogey on the 17th left him one behind Rose at 11-under-par 199.
Rose struggled out of the gate with a bogey on the first. That was his first bogey on the week, and not his last. After three pars, he dropped another stroke on the fifth at the TPC at River Highlands.
The 25-year-old fought back with a 7-foot birdie putt on the sixth to get back to minus-11. Rose missed the green long and left at the par-4 seventh. No matter, as he putted the ball through the chipping area with his 3-wood and rolled it into the cup for birdie.
After a pair of pars, Rose again lost his second shot long, this time left of the 10th green. He blasted a chip shot through the trees onto the fringe, but he was unable to save par from there.
Rose got back to 12 under as his 9-iron approach to the 12th stopped within 3 feet of the cup. He kicked that in for birdie, but more trouble loomed.
After a three-putt par on the par-5 13th, Rose found a greenside bunker with his approach at the 14th. He was unable to save par and he fell to minus-11 and a tie for the lead with Curtis.
Rose came right back to roll in a 10-foot birdie try on the 15th. Curtis matched him, though. Rose two-putted for par on 16 and 18, while getting up and down for par on 17 to close with three straight pars.
'I'm very happy. This is the first time I've had a chance to win this year and I'm enjoying it,' said Rose, who has won four times overseas. 'We separated ourselves a little bit, but somebody always makes a run, so you have to expect that.'
Rose leads after three rounds for the first time in his PGA Tour career.
'I had the lead the best part of Friday and Saturday and I'm comfortable with it on Sunday,' Rose said. 'So I might as well have it now. Sleeping on it shouldn't be too much of a problem.'
Curtis, meanwhile, opened with a birdie on the third. The 2003 British Open winner got within two shots of Rose with a birdie on the seventh.
The 28-year-old Curtis reeled off five straight pars around the turn. After laying up at the par-5 13th, he got up and down for birdie from 98 yards out to move within one of Rose.
Curtis found himself tied for the lead as Rose bogeyed 14. Curtis ran home a 10-foot birdie try on 15 to match Rose's birdie.
However, Curtis lost his tee shot right off the tee at the 17th and found water guarding the fairway. After taking his drop, he knocked his third to 20 feet, but could only two-putt for bogey to end on shot shy of Rose.
Darron Stiles, who was the first player on the course, fired a 7-under 63 to move into seventh place at 7-under-par 203. Tim Petrovic and Kevin Sutherland are one stroke further back at minus-6.
Michael Putnam, who turned professional this week instead of playing in the U.S. Amateur, struggled to a 1-over 71. He shares 10th place at 5-under-par 205 with Darren Clarke, Brad Faxon, Spencer Levin, Spike McRoy and Nick Watney.