Hoffman, looking to atone for last year's collapse when he squandered a two-shot lead with two holes to play, turned a steady start of five straight pars into a sensational round, carding five birdies and two eagles over the final 13 holes.
Compatriot Hunter Mahan, fresh off a share of fourth place at the US Open, was alone in second following a bogey-free, eight-birdie 62 while big-hitting Bubba Watson sits third following an entertaining 63.
Hoffman came to the 17th tee in last season's event at TPC River Highlands with a two-shot lead over Marc Leishman's clubhouse number but double-bogeyed to drop into a tie before making bogey on 18 to hand the Australian the win.
"Believe it or not, I was thinking about (last year) going down 16, 17, 18," said Hoffman, whose round included a course record-equalling back nine of 28. "If I could have just gotten those balls in play, I would have been defending champion here.
"But this year, I got off to a good start and was obviously a little more focused on those last two holes. Hopefully I'm there again this year."
Americans Webb Simpson and Zach Johnson were among six players in a tie for fourth following 65s.
US Open champion Justin Rose of England was in a tie for 18th with a respectable three-under 67 that followed a whirlwind few days doing the talk show circuit to discuss his breakthrough Major win at Merion.
He admitted that being introduced as the US Open champion on the opening tee gave him a real buzz, even if it shook his focus a tad and left him two-over through six holes.
"I got to the first tee and there was such a nice crowd assembled there and I felt really calm and ready to play golf today," said Rose.
"I felt focused and then that happened and I couldn't help a smile come over my face and it truly was a sweeter moment than I thought it would be."
Watson, the 2010 champion and a runner-up here last year, entertained the crowd with seven birdies and an eagle but also had two early bogeys.
The 2011 Masters champion's round was highlighted by a stunning three-wood off the tee on the par-four 15th to just six-feet and a subsequent eagle putt.
Defending champion Leishman shot 68 and was among eight players in a tie for 10th.
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- Bubba Watson
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