In pursuit of a maiden PGA Tour victory in his 50th career start, Berger posted a 10-under total of 200 with fellow Americans Mickelson (68), Steve Stricker (66) and D.A. Points (64) tied for second.
"I'm very satisfied," Berger, the PGA Tour's rookie of the year last season after two second placings among 13 top-25 finishes, told reporters.
"I drove it really well. I kind of picked my way around the golf course really well and hung in there even after a late double bogey that could have turned a good round into a really bad round.
"Made some nice birdies down the stretch and I had fun out there," added Berger, who comfortably two-putted for birdie at the par-five 16th and chipped in from 25 feet at the par-four 17th.
Mickelson, seeking his first PGA Tour title since the 2013 British Open, briefly tied Berger for the lead when he birdied 16, but he bogeyed the 17th after missing the fairway off the tee and did well to scramble for par at the last.
The left-hander, a 42-times winner on the tour, felt his ball-striking still needed improvement.
"Hopefully I'll find it for tomorrow's round because it's only going to take a few more fairways hit and a few more birdie opportunities the way I'm putting to try to get this done," said the 45-year-old Mickelson.
"The rhythm has been a little bit quick. I'll work on it. It's not far away."
Ten players will start Sunday's final round no worse than five shots off the lead, including multiple PGA Tour winners Mickelson, Stricker and Boo Weekley.
Berger, however, oozed quiet confidence despite holding his first 54-hole lead on the U.S. circuit.
"If it was Tiger Woods behind me, I would have the same mentality," said the 23-year-old Floridian. "It doesn't matter.
"The golf course doesn't know who is playing it so I'm just going to go out there and be aggressive and have some fun."
(Reporting by Mark Lamport-Stokes in Los Angeles; Editing by Larry Fine)
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