American Piercy, chasing his first win since the Zurich Classic in April, shot a seven-under 65 for a nine-under total of 135 at the Nine Bridges course on Jeju island, with three-times major champion Koepka one behind in outright second.
Overnight leader Chez Reavie shot a 70 to remain in touch, three strokes behind Piercy in third place.
After high winds played havoc with the expected contenders on Thursday, the field enjoyed gentler weather and most feasted on the course.
Piercy's downhill putt on the par-five ninth, his last hole, gave him his seventh birdie of a bogey-free round.
Compatriot Brian Harman went two birdies better, rolling in nine during the day's best score of 64 to finish in a group tied for sixth on four-under.
Koepka, who skipped the first two stops of the new season, hammered his second shot to five feet from the pin on the 568-yard 18th and rolled in an eagle to briefly grab a share of the lead.
"I'm excited to start the season off," said Koepka, who claimed two of the four majors in 2018 and was the U.S. tour's player of the year.
"(My swing) was dialled in today, I guess.
"I'm hitting well, making putts, I felt like I probably could have shot seven or eight-under there on the front side but I missed a couple.
"But I'm doing everything right and that's what you've got to do."
Koepka's playing partner and defending champion Justin Thomas also eagled the hole to finish with a 70 and a tie for 22nd, eight behind Piercy.
It was scant consolation, however, after a shoddy front nine featuring back-to-back bogeys at the eighth and ninth holes, and another dropped shot at four.
"I just putted terribly for two days," the former world number one said.
"So I haven't exactly played great, but if I'd have just putted average I feel like I'd have got a lot better chance."
Swede Alex Noren shot a 65 to lie four off the pace, tied for fourth with Briton Ian Poulter, an island of European defiance in a leaderboard dominated by Americans.
(Reporting by Ian Ransom in Melbourne, Editing by Sudipto Ganguly)
