Mickelson shot a 5-under 66 in the second round and finished 36 holes at the TPC-Scottsdale course with a 36-hole total of 126.
That performance was marred, however, by a tee shot into the water at the par-4 18th. The resulting double bogey cost him a chance to produce the lowest 36-hole score in the history of the PGA Tour.
Mickelson ended his first round on Thursday with a disappointment as well when his birdie putt lipped out, costing him a chance to shoot 59.
Nevertheless, Mickelson's opening two rounds left him in front of 2011 FedEx Cup winner Bill Haas, whose 64 put him at 129. Keegan Bradley shot a 63 Friday to tie Brandt Snedeker for third at 130. Snedeker won the FedEx Cup title last year.
Mickelson parred each of the first six holes in the second round, then made five birdies in a seven-hole stretch. He reached 7-under for his round when he hit his second shot at the par-5 15th to within four feet of the cup and made the putt for an eagle.
Mickelson has praised a new driver he has used this week, but instead of using that club for his tee shot at the closing hole he hit his 3-wood for safety in hopes of avoiding the water on the left side of the fairway. That plan backfired, however, when his tee ball on the 438-yard hole headed left and found the hazard.
It took a score of 4-under 138 to survive the 36-hole cut and among those who missed it was Rickie Fowler, who was paired with Mickelson for the first two rounds.
Russell Henley and Brian Gay, winners from earlier in the tour season, both survived to play on the weekend. So did Bubba Watson, the 2012 Masters champion who returned to the tour this week after two weeks of illness.
Swim Week Miami Beach 2014 [PHOTOS]