Overnight leader Charles Howell III three-putted for bogey at the last to join Brad Faxon, Fred Funk and Tom Pernice, Jr. in a tie for second at 5-under-par 205.
Tanaka, who held the lead after the opening round, found himself one shot back to start the day at Hamilton Golf & Country Club. He wasted little time in recapturing the lead on Saturday and hit his second shot to six feet for a birdie at the second.
The 32-year-old dropped his approach inside 12 feet for a birdie at the third and made it three in a row with a 10-footer at the par-5 fourth.
At the par-4 fifth, Tanaka left himself within 20 feet of the cup for his fourth consecutive birdie and drained the putt to burst into the lead at 8-under par.
Tanaka came back to the field with a bogey at the seventh but he responded with a long birdie putt at the par-3 eighth. Tanaka found trouble again with a bogey at the par-4 ninth, however, and his problems continued around the turn.
He missed a four-foot putt for par at the 10th and missed the green with his approach at the 11th. Tanaka failed to get up-and-down for his third straight bogey, but he still had some tricks left up his sleeve.
Tanaka ran home a 25-footer for a birdie at the 16th to regain the outright lead at minus-6. At the par-5 17th, Tanaka bounced his second shot in front of the green and watched as it rolled inside eight feet of the hole.
Tanaka ran home the eagle putt to reach 8-under and secured the 54-hole lead despite a bogey at the last.
'It's been about four or five years since I've been in this position on the third day,' said Tanaka through an interpreter. 'So I'm looking forward to it because it's been a while.'
The native of Japan will be in search of his first career victory on the PGA Tour.
'Of course, I want to be in the lead so I don't have to worry about that situation, standing on the tee on 18 tomorrow,' he said. 'I just feel I'll be more happy being in that position at the time on the 18th hole. Even if I don't play well on the 18th tomorrow, just being in that position where I have a chance to win is exciting.'
Howell had a quiet front nine with a lone birdie at the par-5 fourth after his third shot stopped within inches of the cup.
The 24-year-old stumbled with a bogey at the 11th after he missed the putting surface with his second shot but Howell was able to counter at the 17th.
Howell left his second shot short of the green at the par-5 but he chipped to a foot for a tap-in birdie. He gave that shot back at the very next hole, however, when the difficult 18th green cost him a three-putt bogey.
Bob Tway finished alone in sixth place at 4-under-par 206.
Vijay Singh, who opened with a 75 on Thursday, fired a 65 on Saturday to move into a tie for seventh. Singh was joined by Steve Allan at 3-under-par 207.
Local favorite Mike Weir was one shot further back at 2-under-par 208 along with K.J. Choi, Chris Riley, Dennis Paulson, Paul Goydos, Garrett Willis, Mike Springer and Loren Roberts.