Griffin, whose longtime caddie Peter Beck died suddenly about a month ago, had seven birdies on some forgiving greens after a large amount of rain fell on the course the previous day.
He had a one-stroke lead over John Senden and was two strokes ahead of Alistair Presnell.
Australian Masters champion Stuart Appleby, Geoff Ogilvy, Peter Senior, Marc Leishman and Rod Pampling – all Australians – were among a group of nine players at 4 under.
American John Daly held a share of 13th place after carding 69, while five-time champion Greg Norman opened with a 74.
Daly said the course, which had undergone a number of changes – trees removed for a more exposed front nine, and more undulations on the greens – played well.
“The course is in great shape,” Daly said. “The fairways are perfect, it didn’t even look like it rained. It’s a tribute to how they redid the irrigation here.
“I don’t have mud on my shoes or anything,” he said. “That’s pretty impressive after all the rain we’ve had.”
Norman set up a birdie at the par-5 14th hole from an unlikely position. From out of the sand and with an awkward stance, Norman hit a rescue club about 200 yards over the water and two-putted for birdie, drawing applause from playing partner and 2011 Presidents Cup rival captain Fred Couples, who shot a 72.
But Norman had a double-bogey seven at the eighth, his 17th hole of the day.
Griffin had no such problem.
“Almost the most pleasing thing is not having any bogeys,” Griffin said. “Standing over the little three-footer at the last, I was really feeling it.
But, “You’ve got to take advantage of the nice conditions in the morning.”