Koepka, who won two of last season’s four majors and was named the US tour’s player of the year, is on 13-under 203 for the tournament, with compatriot Scott Piercy (72) and England’s Ian Poulter (68) tied for second on nine-under.
Victory for Koepka on Sunday would see him replace Dustin Johnson as world number one for the first time.
Spaniard Rafa Cabrera Bello jumped into contention with a 65 and sits in a group tied for fourth place on eight-under, while Jason Day and Ted Potter Jr also shot 65s to move into a tie for 10th spot, a stroke further back, alongside Ryan Armour (69).
Tiger finally out of the Woods after five years
Marc Leishman (68), a winner in Malaysia last week and CJ Cup runner-up last year, stands on two under, one shot better than Justin Thomas, who beat the Australian in a playoff in 2017 to win the inaugural CJ Cup.
After skipping the first two stops of the new season, Koepka looked out of sorts on the southern island of Jeju with a first-round 71 on Thursday but was back to his best the following day with a 65.
His unblemished card on Saturday could have been even better had a tentative eagle putt at the last dropped instead of sliding by.
Koepka had an earlier chance for eagle at the 353-yard par 4 14th but after his crunching drive made the green his first putt raced by and he was relieved to see the birdie drop coming back.
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