The 27-year-old Koepka closed the tournament with an 18-hole score of 67.
It also marks the seventh consecutive major that has crowned a first time victor.
Koepka entered Sunday in a three-way tie and a shot behind 54-hole leader Brian Harman. He earned $2.16 million, his nation's championship and the comfort of knowing the far-flung trips to Kenya and Kazakhstan and India and beyond are all in the rearview mirror.
"It's definitely a special moment", Koepka said shortly after completing his final round of 5-under-par 67. "You never know how you're going to react being up there in the final round, you've got to deal with that and it's all new for me". "It hasn't sunk in, obviously, and (it) probably won't for a few days".
Harman's bogey on the par-4 12th put Koepka ahead to stay.
Heads up...eyeing two systems in the tropics
Should the tropical system form on the eastern side of the Yucatan Peninsula it would have a greater chance of moving northward. An unorganized tropical disturbance in the Western Caribbean Sea continues to drift toward the Gulf of Mexico.
"To finish in double digits under par at a major championship, especially the Open, it was a good week", Fowler said.
16 Under par for Koepka, tying McIlroy in 2011 for lowest 72-hole score to par in tournament history.
Koepka was the first to strike, making a birdie on the first to go to 12 under and take a share of the lead. Check and check As we have a new USA open champion.
However, Harman eventually stumbled with back-to-back bogeys on 12 and 13 and his rival found peak form at the flawless moment - birdieing three holes in a row from the 14th to all but wrap up the tournament.
Stricker was rolling down the back end of the back nine, with three birdies between the 14th and 17th holes. "He went and won the golf tournament on the back nine". "I've done it before, but he did it today". "The way I putted this week was unbelievable. But I'm happy with the way I played, and it gives me confidence going forward". "I think today he's proven what kind of talent he has, to go out there and play the way he has on a Sunday in a major". He had three bogeys and two birdies on back nine, finishing with a 1-under 71. He had six birdies and one bogey in an exhibition of steady play.
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"That par save was massive on 13", Koepka said.
"I've worked my tail off over the last six months, made some changes, from grinding every day in the gym, trying to make sure that I was physically ready and strong enough to be able to swing the club the way I wanted to", he said.
McIlroy and McDowell both failed to make the cut at the tournament in Wisconsin.
Justin Thomas, who shot a 9-under 63 on Saturday-a record in relation to par-to reach Sunday's final pairing while in a second-place tie with Koepka and Fleetwood, struggled in the final round with a 3-over 75 and tied for ninth at 280.
Brooks Koepka, a strapping Floridian with wowing golf talent, a cool disposition, an athlete's cocksure gait and a two-year place at the fringe of the bright lights, surged from that fringe on a blustery Sunday at Erin Hills.
Birdie - Brooks Koepka: The 27-year-old played the round of his life at the flawless time, firing a 67 to win by four shots. Only four left-handers-Bubba Watson, Phil Mickelson, Mike Weir and Bob Charles-have won major championships.
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Vargas followed up to notch Chile's second in the 90th minute and wrap up the points in Group B's opening match. Chile were without first choice goalkeeper , Claudio Bravio, while Alexis Sanchez started on the bench.
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