Just four strokes covers the top 41 players on a congested leaderboard, that includes world number one Scottie Scheffler who finished with two birdies to sign for a level-par 70.
Dustin Johnson, the 2016 US Open champion shot a 68 but fellow LIV Golf competitor Phil Mickelson had a day to forget after slumping to an eight-over 78.
Both players have been suspended by the PGA Tour for joining the new LIV Golf series, although the United States Golf Association, which runs the US Open, has allowed them to compete this week.
Six-time US Open runner-up Mickelson endured a miserable round on his 52nd birthday. He had just one birdie against five bogeys and two double bogeys to leave him struggling to make the cut in the only major he is yet to win.
Hadwin's 66 is his lowest score in a major in 63 rounds, and the first time the 34-year-old has led after any round of any of men's golf's four biggest tournaments.
A flurry of five birdies in six holes on the front nine saw Hadwin hit the turn in 31, and he held on nicely down the tougher back nine with just one birdie and one bogey seeing him end the day at the top of the leaderboard.
"I was at ease, which is a nice feeling at the US Open as it doesn't happen very often," Hadwin told Sky Sports after his round.
"I had a good run there on the front nine but I knew there would be some tough holes coming home so it was just a case of hanging on."
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