[3] O'Meara was born in Goldsboro, North Carolina, but grew up in southern California, specifically in Mission Viejo.

[9] After graduating with a degree in marketing in 1980, O'Meara turned professional and would win 16 events on the PGA Tour, beginning with the Greater Milwaukee Open in 1984, and the AT&T Pebble Beach National Pro-Am five times.

His best year as a professional golfer came relatively late in his career – in 1998 at age 41 – when he won two majors: The Masters and the British Open.

O'Meara is known for competing outside the United States more often than most leading American golfers, and has won tournaments in Europe, Asia, Australia and South America.

After the European Tour tournament Lancome Trophy at Golf de Saint-Nom-la-Bretèche, 30 km west of Paris, France in September 1997, which was won by O'Meara, he was involved in a controversy.

O'Meara insisted he had not intended to gain any advantage and sought advice from the PGA and European Tours, who informed him that the tournament was over and the result stood.

O'Meara was sidelined by a rib injury for several months starting in April 2012; he missed the majors on both tours and did not compete until August.

O'Meara retired in September 2024 after the PURE Insurance Championship, having announced that it would be his last professional event, and missing the cut.