Koepka and DeChambeau share the lead after matching six-under-par 66s, sitting a shot ahead of Mickelson, who is bidding to write history by becoming the game’s oldest major winner.
Koepka is making a habit of putting his name at the top of leaderboards in golf’s biggest events. The 28-year-old has won two of the last three majors and three of the last six he’s played in.
A wrist injury forced him to watch this event from his couch at home in Florida 12 months ago. He returned to action with a vengeance to become the first player in nearly 30 years to win the US Open back-to-back then added the US PGA Championship.
Koepka, who has never looked back since winning the Scottish Challenge in Aviemore in 2013 to secure a step up to the European Tour before switching his attention to the PGA Tour, is off and running again on one of the game’s showpiece stages.
He signed for six birdies, including four in a row from the 12th, in a bogey-free effort as he matched the clubhouse target set shortly before by fellow American DeChambeau.
“I treat these events a lot different than regular PGA Tour events in terms of preparation,” said Koepka afterwards, “and four birdies in a row on the back nine usually helps in getting off to a good start.”
DeChambeau, who was the leading amateur here on his debut in 2016, finished with four straight birdies - and that late burst could easily have been six-under.
The 25-year-old was inches away from making a hole-in-one at the 16th then hit the flagstick square on with his second shot at the 18th only to see it stay out as it cannoned backwards.
“I should have pulled the flagstick,” joked DeChambeau, who is one the players that have been keeping it in when putting after that rule change was introduced at the start of this year.
“But that’s all right after making four birdies to finish. I had to be patient on the front nine and from the 15th hole on I sailed through.”
Three-time winner Mickelson is lurking ominously after carding five birdies in the last seven holes to match the opening score from his 2010 victory.
Repeating that success on Sunday will see Mickelson claim the record as golf’s oldest major champion from Julius Boros. He was 48 years and four months when winning the 1968 US PGA Championship whereas Mickelson is 48 years and 10 months.
“It was great,” said the 2013 Open and Scottish Open winner of his day’s work. “It’s fun to finish a good round off rather than leak one here or there coming in.
When you have a good round going, you hate to let one leak here or there coming in and I didn’t do that today. I finished it off. So it was a good day.”
Also among the later starters, Ian Poulter and Dustin Johnson sit joint-fourth on 68, one ahead of a group that includes 2013 champion Adam Scott and recent WGC-Match Play winner Kevin Kisner.
“I’m very happy with today’s work,” admitted Poulter after making his move with three birdies in four holes on the back nine. “My whole game was together.”
Four-time winner Tiger Woods is in a group on two-under that also includes Open champion Francesco Molinari and Rickie Fowler, last year’s runner-up.
Patrick Reed, the winner 12 months ago, had a 73, as did 2017 champion Sergio Garcia and also Rory McIlroy, who needs a Green Jacket to become just the sixth player to complete a career grand slam.
It was a disappointing day for world No 1 Justin Rose as he had to settle for a 75, the same score posted by Masters specialist Jordan Spieth after he went out in 40.
Paul Casey, who came into the event with high hopes after his recent win on the Valspar Championship on the PGA Tour, is second last in the 87-man field after a nightmare 81.