A tie for second place by Tiger Woods enabled Mickelson's fellow American to regain the lead from Australia's Greg Norman.
Mickelson, who began the final round with a one-stroke lead, recovered from a first-hole bogey to shoot a four-under-par 68 on the saturated La Costa course. He finished at a 17-under 271, while Woods and O'Meara both shot 64 to tie for second on 272.
"It was a pretty exciting day and a great way to start '98, because '97 in some respects was disappointing for me, even though I won two times," Mickelson said. He collected $306,000 (pounds 204,000) for his 12th PGA Tour victory.
Mickelson, who grew up in nearby San Diego and used to attend this tournament regularly, was not at his best, but seven birdies and three bogeys were enough to achieve his goal.
"I had one mindset," he said. "The only thought I had was to do whatever it takes to win and I kept thinking that throughout the round."
Woods, the defending champion, could not quite repeat, but he did enough to show everyone he is likely be the player to beat again this year.
"I drove it great all week, hit my irons well," he said. "Unfortunately I had a four-putt and two three-putts. Other than that I'm very pleased with my game. All the things I've been working on feel very comfortable."