Fowler and world number six Schauffele fired matching eight-under-par 62s that marked the lowest round in US Open history and equalled the lowest major round of all time.
"I knew there were birdies to be made out here, but you have to drive it well and get the ball in position first," Fowler said. "Yeah, did that, and from there just managed our way around really well."
The American wasted little time making his move as he birdied his opening hole, the par-four 10th, and reached the turn in three-under 32 before a flawless trip through his closing nine holes during which he carded five birdies.
Schauffele, who has five top-10 finishes in his six U.S. Open starts, also got off to a flying start with three birdies across his first five holes while avoiding a bogey all day at an event that prides itself as being the toughest test in golf.
"It's not really what you expect playing a US Open. But monkey see, monkey do," Schauffele said. "Was just chasing Rickie (Fowler) up the leaderboard. Glad he was just in front of me."
In the afternoon wave, LIV Golf's Johnson was enjoying an unblemished round until a par putt on his last hole lipped out, leading to his lone bogey of the day.
"It was a little rude that that one didn't go in, but obviously I swung it really nicely today and hit a lot of good shots," Johnson said.
Wyndham Clark drilled a long birdie putt on 18 to grab a share of third place with Johnson after firing a round of six-under 64.
World number three McIlroy started red hot, covering his front nine in five under par with help from some thunderous drives.
But he whiffed on a chip shot from the thick greenside rough on 18, managing to avoid a double bogey with a nice putt to end his day.
McIlroy has a share of fifth place with Brian Harman who, like the Northern Irishman, got off to a stellar start before cooling off on the back nine.
'GOOD NUMBER'
World number one Scottie Scheffler said he was pleased with carding a 67 even though he bookended his round with bogeys.
"Hit a lot of good shots today and I did a good job of staying patient out there," he said. "Posted a good number on a day in which I got off to a pretty slow start."
Masters champion Jon Rahm, looking to become the first player to win five times in a season since Justin Thomas in 2016-17, also went out early and carded a one-under 69 after mixing three birdies with a pair of bogeys.
Viktor Hovland, the only player to finish in the top 10 in each of the last three majors and in his first start since his Memorial triumph 11 days ago, also opened with a 69.
PGA Championship winner Brooks Koepka and defending US Open champion Matt Fitzpatrick both got off to slow starts and laboured to a pair of one-over 71s.
As the US Open got underway, a report surfaced that the U.S. Justice Department would review the PGA Tour's plan to form a unified commercial entity with Saudi Arabia's Public Investment Fund, which controls LIV Golf.
Phil Mickelson, who was the first big name to join LIV when it launched amid a cloud of controversy, declined to comment on news of the Saudi partnership, which rocked the sports world when it was announced last week.
"Not yet because I don't want to detract right now from this tournament and where I'm at," Mickelson said after carding a 69.
"I'm playing well. I want to get myself in contention. I'll talk about it maybe after."
