Pettersson, fresh off a tie for third at Kiawah Island in the year's last Major, had eight birdies to sit one shot clear of American David Mathis and South African Tim Clark at Sedgefield Country Club.
"I started off the round good with two birdies in the first three holes and got me kind of straight back into the score mode from last week," said Pettersson.
"I hit it pretty good off the tee and hit my irons good and putted really well. It was a great day for me."
Americans Tom Gillis, Troy Matteson and Scott Stallings were tied in fourth place after shooting matching 64s in the final event before the FedEx Cup play-offs begin next week.
Defending champion Webb Simpson, who captured his first US PGA title here last year, was among a group of 12 golfers sitting four shots off the pace.
Clark and Pettersson both played college golf for nearby North Carolina State and used their local knowledge to full effect at Sedgefield.
Pettersson, the 2008 champion of the event, opened on the back nine and rolled in a six foot birdie on the 11th to kick start his round.
He drained 17-foot birdie putts on the 12th and 16th holes before converting a shorter eight-foot try on the 18th to turn four under.
A run of four pars failed to give an indication of the blitz to come but Pettersson drained four consecutive birdies from the par-five fifth to take the outright lead.
Pettersson is already assured of a deep run through the play-offs, entering this week in ninth position, but for others this is the last chance to get inside the top 125 to make it to the Barclays next week.
Mathis started the best of those outside the mark, with a second place projection moving him from 136th to 86th.
"It's nice to get off to a solid start, give myself an opportunity to go forward to have a good finish and get in those playoffs which, gosh, it's a pretty big deal," said Mathis.
Jason Bohn (70) and Jhonattan Vegas (71) need improvement on Friday or they are projected to fall outside of the mark.
Former major winners Yang Yong-eun, John Daly and Angel Cabrera are all still projected outside the top 125 although Yang's 67 gives the South Korean a base to make a late push.