The golfer from Santiago shot nine birdies against a lone bogey to stand on 12-under 130 after 36 holes at TPC Summerlin in Las Vegas.
"I had a really good round overall," Pereira said. "I hit driver well, irons really good. I hit three or four shots inside three feet. Solid on my putting. Overall really good and happy how I played."
American Robby Shelton carded a bogey-free 63 to swipe second on 131.
South Korea's Kim Joo-hyung and Kim Si-woo and American Maverick McNealy shared third on 132 with Australian Cam Davis while Americans Chad Ramey and Kevin Streelman on 133.
Pereira, Davis and the Kims are among six members of captain Trevor Immelman's Internationals team that lost to the United States two weeks ago at the Presidents Cup.
"Trevor did a really good job with us, encouraging us how good we are, how good we play golf, so we carry that over here," Pereira said. "Right now we're playing really good.
"He just really tried to put us in a position that we really want to play well and really trusting ourselves. Every day he did like a little speech of how good we are and how we can do this. So I think it really touched us."
Pereira seized his first PGA lead since he was ahead at the final hole of the PGA Championship in May at Southern Hills only to double bogey and finish in a share of third.
"It's just way over there in the past," Pereira said of his PGA Championship memory. "I'm just trying to get my first win here.
"Hitting off the tee good and irons are going to be very important. You've got to go pretty low this week, so just keep doing what I'm doing."
Pereira began on the back nine and put his approach inches from the hole at the par-5 13th and reeled off five birdies in six holes starting at the 15th, four birdie putts from six feet or less plus a 15-footer at the second hole.
He birdied the fourth from inside six feet, dropped his approach inches from the hole to set up a birdie at the sixth and then answered a three-putt bogey at seven by closing with a six-foot birdie at the par-5 ninth.
