The American entered the final day one shot behind overnight leader Brian Harman and the two were engaged in a real battle for the title before Koepka made three birdies in a row from the 14th to move clear at 16 under.
Harman signed for a 72 to emerge as the closest challenger alongside Japan’s Hideki Matsuyama, one shot ahead of England’s Tommy Fleetwood, who also carded a closing 72.
The victory is Koepka’s second on Tour after the Turkish Airlines Open in 2014, a season in which he finished eighth in the Race to Dubai Rankings presented by Rolex.
His 16 under par winning total also matches the US Open record of Rory McIlroy when he won his first Major at Congressional in 2011.
“I was way more confident this week than I’ve ever been, I felt like I was striking the ball really well, I was putting the ball in the fairway - which you need to do out here - and then I was putting so well,” he said.
“It’s for all the hours that you put in and things like that. You look back a couple of years ago to be on the Challenge Tour, four guys driving around in a little mini car, four golf bags packed in there, to be the US Open champ is pretty cool.
“To go over to Europe and kind of cut your teeth over there and be able to play in different conditions is what you need to do.
“I built on those wins on the Challenge Tour, any time you can win you’re going to have confidence and I look back at those.”
Koepka took advantage of the first to join Harman at 12 under and when he played a chip to close range at the second, he was out in front on his own.
Harman needed to make smart par saves on the first and second as the overnight leader showed signs of nerves but he rolled in an excellent 29-footer on the third to reclaim a share of top spot.
Koepka holed from 34 feet on the eighth to hold a one-shot lead at the turn but a three-putt at the tenth dropped him back into a share as he and Harman could not be separated.
Matsuyama had taken advantage of the par five first, holed a 41-footer from the fringe on the fourth and then put his approach to tap-in range on the next to get to nine under.
A dropped shot on the sixth stalled his momentum but putts of 11 and 19 feet on the 11th and 12th all of a sudden moved him into double figures and three shots back.
Harman found some nasty rough on the 12th to drop out of the lead but Matsuyama was moving in the other direction, going birdie-bogey on the 14th and 15th but then putting his tee-shot to 11 feet on the next.
A closing gain saw him set the target but when Koepka played a stunning bunker shot to birdie the 14th and Harman three-putted the 13th, the 27-year-old was in the driving seat.
Harman bounced back with a birdie on the 14th but Koepka put his approach on the 15th to ten feet to maintain his cushion and a 17-foot putt on the next made it three birdies in a row and a four-shot lead.
A front nine of 37 proved to be Fleetwood’s downfall and while a birdie on the 14th kept his hopes alive, he too succumbed to Koepka’s surge.
Americans Rickie Fowler, Bill Haas and Xander Schauffele were at ten under, a shot clear of Charley Hoffman and two ahead of Trey Mullinax, Brandt Snedeker and Justin Thomas.