The Swede finished with a 6-under-par 66 at the Ocean Course on Kiawah Island, S.C., with a scorecard that included six birdies and no bogeys.
"Obviously getting off to a good start was the key to the round," Pettersson said.
The wind at Kiawah Island laid low early in the day, which allowed Pettersson to get off to a fast start. The breeze picked up later in the day, but 44 players still managed to break par.
Tiger Woods was among a crowd at 3-under. Woods birdied his first two holes but had consecutive bogeys on 13 and 14.
Conditions were expected to deteriorate Friday with wind gusts up to 30 miles per hour forecast.