Reed moved within sight of his fourth victory in 10 months with an even-par 71 on the brutally tough Congressional course in Bethesda just outside Washington D.C.
The American posted a six-under 207 total, while Australian Marc Leishman (73), Swede Freddie Jacobson (71) and South Korean Noh Seung-Yul (66) were equal second on four-under.
Six others, including last year's US Open champion Justin Rose, were three strokes behind.
Australian Oliver Goss, who shared the halfway lead in his second tournament as a pro, got a reality check to fall five shots behind with a 76 that included a double bogey at the par-four 12th, where he missed a putt from barely 18 inches.
Reed has enjoyed a meteoric rise since his maiden PGA Tour victory in a playoff against Jordan Spieth in Greensboro, North Carolina, last August.
He made headlines after his third win, at the WGC Cadillac Championship in Miami in March, when he said he was one of "the top five players in the world".
But the 23-year-old has not backed up his words since, missing five cuts in eight starts before this week, perhaps due partly to the distraction of the recent birth of his first child.
He currently is ranked 29th in the world and is a noted front runner, having converted all three of his 54-hole leads into victories.
"I'm in great position," Reed told CBS television, adding that he needed to 'tighten up' a few aspects of his game before the final round.
Jacobson made his move with four front nine birdies, only to drop four shots in four holes on the tough stretch starting at the 10th.
"I played awesome on the front nine," he said.
So did Noh, a winner in New Orleans in April, who charged into contention for his second tour title with the best round of the day on a course where punishing rough and firm greens made birdies a prized commodity.
Congressional has hosted three U.S. Opens, most recently in 2011 when Rory McIlroy won, but it is playing tougher this week due to the dry conditions.
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