Woods, playing his final tuneup for next week's last major tournament of the year at the PGA Championship at Oak Hill, fired an eagle and seven birdies to finish 36 holes on 13-under 127.
"I'm very happy I was able to post that," Woods said. "I just kept thinking, whatever lead I had, let's just keep increasing it. It's at seven now so that's not too bad after two days."
"Disappointed? Absolutely not," Woods said. "A 61 is pretty good. I'm not bummed."
England's Chris Wood and American Keegan Bradley shared second on 134 after each fired a 68. Sweden's Henrik Stenson and American Bill Haas are fourth on 135.
Aside from two at Firestone, Woods fired his other 61s at the 1999 Byron Nelson Championship and the 2005 Buick Open.