The American left-hander, who says he is in the best form of his career, started at the 10th but followed an opening birdie by dropping a stroke two holes later on the Blue Monster course.
Mickelson drove out of bounds at the 12th before rallying with six birdies, including an excellent chip-in at the par-four seventh, to finish on 13-under 131.
Tiger Woods, playing his first strokeplay event after his eight-month layoff for knee surgery, returned a 70 for 141.
The world number one started well with birdies at the first and fourth. He dropped back with bogeys at the sixth and 10th before recovering with two birdies at the 12th and 17th.
Mickelson leads by two shots from compatriot Nick Watney, who carded a bogey-free 67.
Experienced American Kenny Perry and British teenager Rory McIlroy were tied for third, three off the pace.
Topsy-turvy
The exciting McIlroy had a topsy-turvy end to his round of 66 after starting at the 10th.Five-under after 13 holes, the Northern Ireland teenager followed bogeys at the fifth and seventh by eagling the eighth and birdying the ninth.
Perry moved into contention with a bogey-free 64, a round matched by Spaniard Alvaro Quiros who finished on 136.
Prayad Marksaeng, who shared the overnight lead, recorded a 70 for 135 after taking seven shots at the par-four 18th.
The Thai hit his tee shot out of bounds before three-putting with his second ball.
India's Jeev Milkha Singh, another of the overnight leaders, was on 136 after bogeying the 17th and double-bogeying the last for a 71.










