The 35-year-old American, ranked 25th in the world, surged to a nine-under total of 133, vaulting past England's Justin Rose who carded a one-under 70 and held the lead at seven-under 135 for much of the day.
It was the second 65 in as many days at Pebble Beach, where Tiger Woods had posted the only prior six-under round in US Open play on the way to his devastating 15-shot victory in 2000.
Woodland, teed off on 10 and climbed the leaderboard with birdies at 12 and 16. After a birdie at the first, he drained a 15-footer for birdie at the par-three fifth to tie Rose, then birdied the par-five sixth for the lead.
Woodland held his nerve at eight and nine, the toughest holes on the course. He saved par from the greenside rough at the eighth and overcame a bad break at the ninth where his tee shot nestled in a small divot in the fairway.
He still managed to reach the green in two, setting the stage for his final putt.
The three-time winner on the US PGA Tour heads into the weekend trying to improve on his previous best finish in a major, a tie for sixth at the 2018 PGA Championship where he also led after 36 holes.
He was tied for eighth at this year's PGA Championship at Bethpage Black.
Rose was alone in second after 36 holes, one stroke in front of South Africa's Louis Oosthuizen, who had seven birdies and six bogeys in a wild one-under 70.
Four-time major winner Rory McIlroy and South African-born American Aaron Wise were a shot back on five-under 137, McIlroy with a 69 and Wise a 71.
Five players were tied at four-under, a group that included two-time defending champion Brooks Koepka, who carded his second-straight 68. He was tied with Americans Chez Reavie, Chesson Hadley and Matt Kuchar and England's Matt Wallace.
However, Thai No 1 Kiradech Aphibarnrat did not make it to the weekend rounds due to his total score of seven over-par-149.
Elsewhere among the late starters, McIlroy had five birdies to offset a bogey and a double-bogey in a two-under 69 for a five-under total of 137, tied with Aaron Wise.