The American, who has three top-10 finishes so far this season, held a one-shot lead over fellow countryman Hunter Mahan after a day of low scores at TPC River Highlands which also saw Justin Rose begin life as a major winner with a 67.
Hoffman was just two under at the turn but holed his second shot at the par-four 10th before hitting a birdie on 12 and another eagle on the par-five 13th.
Two more birdies on the way home saw him move to nine-under and the outright lead.
Hoffman finished second here last year after a disastrous bogey, double-bogey finish and admitted that was playing on his mind down the stretch.
"It's nice to come back after that finish last year," Hoffman told www.pgatour.com.
"Believe it or not, I was thinking about (last year) going down 16, 17, 18.
"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."
Mahan, who started his round on the 10th, birdied his first hole before claiming three in a row on 13, 14 and 15.
A further birdie on 17 got him to the turn in 30 and three more on his back nine saw the 31-year-old record a flawless round as he looks to regain the title he won in 2007.
Mahan also opened with a 62 that week and said: "There are a lot of courses I like, but I haven't had the success I've had here. I think this is the most comfortable course on Tour for me.
"I feel like I have a good sense of these greens. I can read them really well. When you have confidence in what you see, it makes your stroke a lot easier.
"When I birdied the par five (sixth), I thought about the chance to birdie the last three to maybe get to 60 or 59.
"Just had a misread on eight and seven. But I was definitely thinking about it for sure."
Bubba Watson was a further shot back after a spectacular back nine.
The former Masters champion, who won this event in 2010 and was joint-second with Hoffman last year, was two under after nine holes thanks to four birdies and two bogeys.
But he picked up shots on 11 and 13 and then eagled the par-four 15th before a further birdie on 17 put him right in contention.
There was then a group of six players on five under as fellow Americans John Merrick, Webb Simpson and Zach Johnson along with Colombian Camilo Villegas, Australian Rod Pampling and Canadian Graham DeLaet fired 65s.
There was a large group of players on four under which included Ireland's Padraig Harrington with newly-crowned US Open champion Rose and fellow Englishman Lee Westwood in an even larger pack a further shot back.