Ko birdied the final three holes for her third straight 5-under 67 and a four-stroke victory over second-ranked Inbee Park.
A week after finishing second in Phoenix at the Founders Cup, Ko heads to Rancho Mirage for the ANA Inspiration with her first LPGA victory of the year and 11th overall. The 18-year-old New Zealander also won the Ladies European Tour's New Zealand Women's Open in February.
Ko finished at 19-under 269.
Park closed with a 67. The 2013 winner at Rancho Mirage, Park appears to be over the back problem that forced her to withdraw from the first event of the season. The South Korean player tied for 30th in Thailand and Singapore in her first events back and missed the cut in Phoenix.
Playing two groups ahead of Ko, Park pulled within two shots with birdies on the par-4 16th and par-5 17th. Ko pushed the lead back to two with a birdie on the short par-4 16th, holing a 10-foot putt after driving the green and racing her first putt past the hole.
Ko made an 8-foot birdie putt on 17, and finished with a 15-footer on 18.
She bogeyed the par-5 10th after double-hitting a putt from the fringe. The ball popped out of a divot and caught her club in the follow-through, costing her a one-stroke penalty.
Japan's Ai Miyazato was third at 12 under after a 66.
South Koreans Sung Hyun Park and Jenny Shin each shot 72 to tie for fourth at 11 under. Sung Hyun Park received a sponsor exemption.
Brittany Lang closed with a bogey on 17 and a double bogey on 18 - hitting into the water twice - for a 74 that dropped her into a tie for 10th at 9 under.