Mickelson completed the opening 36 holes at 16-under-par 128. That was one stroke better than the old 36-hole record set by Larry Nelson in 1988.
Both of Mickelson's first two wins at this event came in weather-shortened, playoff affairs.
J.J. Henry also fired a 65 in round two to climb into second place at 10-under-par 134. Two-time Masters champion Jose Maria Olazabal is one stroke further back at minus-9 after a 64. Australian Gavin Coles stands alone in fourth place at 8-under-par 136 after an even-par 72 in the second round.
Mickelson got off to a flying start as he birdied 10 and 11 on the TPC at Sugarloaf to quickly jump to 11 under. After a par on 12, he birdied the 13th to keep rolling.
The 2004 Masters champion parred his next three holes before dropping in another birdie putt on the par-4 17th. Mickelson moved to 14 under with a birdie on the first.
The 35-year-old former Arizona State star ran in a birdie putt on the fifth. Mickelson made it two straight with a birdie on six. He parred the final three holes and has played 28 consecutive holes without a bogey.
'Well, it was a fun round. I enjoyed coming out this morning when the greens were fresh and making a couple of putts early,' Mickelson said. 'It was fun to keep the ball in play and feel like I was trying to make birdie every hole rather than fighting for par. Those rounds are few and far between for me, but I love them when they occur.'
Henry opened with back-to-back pars before jumping up the leaderboard with four straight birdies from the third to move to 7 under.
The Connecticut native parred each of his next six holes around the turn. Henry dropped in a birdie on the par-4 13th and made it two straight as he also birdied 14. After three more pars, Henry closed with a birdie at the last. He has gone 26 consecutive holes without a bogey.
Olazabal got off to a flying start with four birdies over his first six holes. After parring his next four holes, the Spaniard collected birdies on 11, 13 and 15 to get to minus-8. He closed with a birdie on No. 18 to close out a bogey-free round of his own.
'I played a lot better than Thursday without question. I made a lot of putts today and that was the key for today's round,' said Olazabal. 'I hit my irons okay. The only area where it was not all that good was the driving. Even though I hit most of the fairways, I did not feel comfortable with it.'
Jonathan Byrd posted a 4-under 68 to get to 7-under-par 137. He was joined in a tie for fifth by Shane Bertsch (69) and Charles Warren (72). Luke Donald, Duffy Waldorf, Ian Poulter and Ryuji Imada were one stroke further back at minus-6.
The cut line fell at even-par 144 with 79 players moving on to the weekend. Among those missing out on the final two rounds were Rory Sabbatini, J.B. Holmes and Olin Browns at 145, Miguel Angel Jimenez (146) and Chris DiMarco (153). DiMarco, a playoff loser to Tiger Woods at the Masters last year, is battling a rib injury.