He posted a 17-under 196 total, while Scott managed a 69 and was joined on 13 under by American Holmes (68).
Thomas was seven strokes clear of anyone else. Big guns Rory McIlroy, Jordan Spieth and Tiger Woods were seemingly too far back to have a realistic chance of victory.
McIlroy (69) and Spieth (70) were eight strokes behind, while Woods trailed by 10 despite a stellar 65.
His score matched Thomas's as the best of the third round.
The Genesis Open is the only event on the PGA Tour that Woods has played at least 10 times without a win.
Former world number one Thomas has already won nine times on the PGA Tour, including a major at the 2017 PGA Championship.
The 25-year-old's most recent victory came at the WGC-Bridgestone Invitational last August.
The final round on Sunday began almost as soon as the third had finished.
Players barely had time for a quick bite on a marathon day after having resumed the third round in semi-darkness at 6.45 a.m. local time.
The tournament was put behind schedule due to a seven-hour rain delay on Thursday.
(Reporting by Andrew Both in Cary, North Carolina; editing by Clare Fallon)
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