Koepka's advantage could have been even greater, only for two late bogeys on day three to give Australia's Adam Scott the chance to close in.
A four-under 66 still keeps Koepka in a strong position, however, with three others - Rickie Fowler, Jon Rahm and overnight leader Gary Woodland - three shots further back as they all chase a maiden major victory.
Woodland had a disappointing round, with a triple bogey on the 10th seeing him relinquish his place at the top of the leaderboard.
Elsewhere, Tiger Woods is still in outside contention thanks to a round of 66 to end on eight-under, while a contingent of four Englishmen are down in joint-21st on five-under.
US PGA CHAMPIONSHIP LEADERBOARD
1. Brooks Koepka (-12)
2. Adam Scott (-10)
3. Rickie Fowler (-9)
= Jon Rahm (-9)
5. Gary Woodland (-9)