Todd Hamilton and Brad Faxon posted matching rounds of 6-under 66 to climb into a tie for second place. They stand at 10-under-par 134, two strokes clear of Fredrik Jacobson (69).
Pettersson opened his round on the back nine on the Sunrise Course at Country Club of Mirasol and sank his first birdie of the day at the par-3 11th.
He then ran home back-to-back birdie putts from the 14th to climb to minus-12, two shots clear of the field.
'I think it's important if you get off to a good start, which I did today,' Pettersson said. 'I birdied my second hole, which was nice, and I just carried on from yesterday.'
Around the turn, Pettersson sank a birdie putt at the first. The Swede then stumbled to his first bogey of the event at the very next hole.
Pettersson erased that mistake with a two-putt birdie at the par-5 fifth before closing with four straight pars.
'Yeah, it's been great. I'm glad I carried on from yesterday, and felt like I played nearly as good as yesterday, but didn't make quite as many putts,' said Pettersson. 'I'm just going to keep doing what I'm doing.'
Pettersson is in unknown territory. By his own admission, he has never held a 36-hole lead before.
'I've never had a 36-hole lead in Europe,' Pettersson admitted. 'I actually don't think I've had a 36-hole lead ever. I've been close in Europe a couple of times, but tomorrow, I'll see what happens.'
Hamilton also started on the back nine and stumbled out of the gate with a bogey on the par-4 10th. He made up for that as he converted back-to-back birdies from the 12th to get to 5 under.
The 38-year-old caught fire around the turn. He dropped in a birdie putt at the 17th and followed with another birdie at the next. Hamilton made it three straight when he birdied the par-4 first.
Hamilton dropped another stroke at the par-3 third. He came right back with a birdie at the fifth and the University of Oklahoma product capped his round with consecutive birdies from the seventh.
'Obviously, I'm very pleased with how I've played,' said Hamilton. 'I've been struggling with my putter and I'm not a big fan of bermuda greens, so I'm very excited and it's kind of unexpected that I'm doing so well, not liking the bermuda greens. But love the course and I just hope to continue playing well.'
Faxon used a scorching front nine to take the lead prior to Pettersson teeing off. Faxon birdied the first, then ran off three straight birdies from the fourth.
He then sank back-to-back birdies from the ninth to move to minus-10. The seven-time winner on tour closed with eight pars in a row.
'That was a good round today, very solid with no bogeys, lots of fairways, lots of greens,' Faxon said. 'I drove it well and I got off to a great start. I birdied No. 1, which kept the momentum going from yesterday.'
Davis Love III (69) and his good friend Fred Couples (70) moved into a share of fifth place at 6-under-par 138. They are joined there by Mark Hensby, Tommy Armour III, Craig Bowden, Jesper Parnevik, Rory Sabbatini, John Senden and Tom Pernice, Jr.
Luke Donald and former Masters Champion Larry Mize pace a group of players at 5-under-par 139.
The cut line fell at even-par 144 with defending champion Justin Leonard surviving on the number.