Homa signed for a final round 66, 6 under par, on the South Course at Torrey Pines to win by two strokes from Keegan Bradley (66) with Collin Morikawa (69) a further shot back on -10.
Homa now has four wins in his last 29 PGA Tour starts and the latest of them, his second of the season, will see him break into the top 15 for the first time in his career.
Overnight leader Sam Ryder began with a two-shot lead and started his final round with a birdie but bogeys on the seventh and eighth a double-bogey at the 15th saw him finish with a 3-over 75 and a share of fourth alongside Sahith Theegala (70) and Sung-Jae Im (70).
In contrast, Homa recorded only one bogey and seven birdies including a run of three in a four-hole stretch from the third having holed out from 25 feet.
"I hope that I haven’t seen my best day yet, my favourite day yet,” Homa told pgatour.com. "I’m sure there will be many other great, great days. Today feels like the best day ever. I hope that tomorrow feels better.
"You’re just hopeful. I think all of us kind of have that. You just hope for the best and stay the course.
“I think I have a great perspective towards my love for this game.
"I've seen kind of all of it. I remind myself most days too when I'm getting nervous coming down the stretch or things are getting wobbly, like today 12, or 13, 14, 15. I just kind of always remind myself, ‘You've seen the darkness of this game, enjoy this, enjoy the beauty of it.’ People chanting my name, things I could never have imagined … I think that it's calming.
“I think everybody out here's got their own chip, everyone out here's got their own story, everyone out here has their own struggles. They look a little bit different. We all handle it how we handle it. But yeah, I can only tell you what's going on in my head, and that's how I've kind of tried to use it.”
