Mickelson, who began the day with a four-shot advantage on South Korea's Kevin Na, maintained his edge with a controlled performance in front of boisterous gallleries at the Tournament Players Club in Scottsdale, Arizona to finish at 17-under 267.
McCarron had the best round of the day, a six-under 65, and vaulted up the leaderboard to finish joint second with Na at 12-under 272.
David Toms, Steve Flesch and Tim Herron finished a shot further adrift at 11-under 273.
An Arizona State almuni, Mickelson enjoyed a distinct home course advantage, every shot cheered on by the raucous Phoenix crowd, which is rated the rowdiest on the PGA Tour.
The lefthander set the stage for his 24th career victory during Friday's second round when he equalled the course record with a sizzling 11-under 60.
Na kept pace with Mickelson early on, opening his round with a birdie at the first but the 21-year-old was unable to close the gap despite finishing with birdies on two of his final four holes to card a two-under 69.
Mark Calcavecchia, a three-time winner here, initially stayed in contention but faded down the stretch and finished with an even par final round, nine shots behind Mickelson on 276.
World number one Vijay Sing closed with a three-under 68 to join a group of eight golfers tied for 11th at seven-under 277.