Mickelson, who led going into the final round, was never seriously challenged on the final day as he cruised to a seven-point victory over the Australian Stuart Appleby in delightful playing conditions at Castle Pines.
He compiled a round of five birdies and one bogey for a four-under-par 68 worth nine points under the Modified Stableford format used for the event.
The scoring system awards five points for an eagle, two for a birdie, zero for par, and subtracts one point for a bogey and three for a double- bogey or worse.
Mickelson finished with 48 points to become the first player to win the title twice in the event's 12-year history. He also beat his own tournament record of 45 points, set in 1993. He recorded two eagles, 21 birdies and four bogeys for an unofficial 21-under 267 total.
"I played four good rounds and that's something I haven't done too much this year. It gives me a bit of momentum going into the PGA Championship," said Mickelson of the year's final major championship in two weeks' time.
The 11th PGA Tour victory of his career and second of the year was worth $306,000 and 150 Ryder Cup points, which pushed Mickelson up from ninth to fifth place in the US standings.
The top 10 players after the PGA Championship automatically gain selection for the American team that will challenge Europe, the holders, at Valderrama, Spain, next month.Reuse content