Starting the final round three shots behind, Kerr was in a three-way tie for the lead at Aviara Golf Club when she pulled away from Mirim Lee and 17-year-old Lydia Ko. Her fourth straight birdie was on the 16th hole when she drove the green and two-putted from 20 feet.
It was her 17th career win, and her first since May 2013 at the Kingsmill Championship.
Kerr's two-shot victory over Lee (70) ended a stretch of seven straight LPGA events won by South Korean-born players dating to the CME Group Tour Championship last year.
''I love to win,'' Kerr said. ''Golf has always been great to me, always given me special moments like this.''
Ko was tied for the lead with a birdie on the par-3 14th hole, but the No. 1 player in women's golf didn't make another birdie the rest of the way. She lipped out on a 5-foot putt on the 16th and finished with a three-putt bogey on the 18th for a 67 to finish third.
It was her 28th consecutive round under par on the LPGA tour, one short of the record Annika Sorenstam set in 2004. Ko's next event is the ANA Inspiration at Mission Hills, the first LPGA major of the year.
''Last three holes were a little iffy, like yesterday, but 67 around here is good and I've improved my placing compared to last year, so a lot of positives to take from this week,'' Ko said. ''And I'm excited for the first major next week.''
Ko had her 10th consecutive finish in the top 10.
Kerr opened up a three-shot lead with her fourth straight birdie. Lee, playing in the final group behind her, drove the 16th green to within 4 feet for eagle to get within one shot. Her next tee shot wasn't nearly as good. She pushed it into the trees and chopped her way to a double bogey on the par-5 17th that effectively cost her any chance of winning.
Kerr finished with a three-putt bogey on the 18th and still broke by six shots the 72-hole record at the Kia Classic, which began in 2010. She finished at 20-under 268.
The 37-year-old American couldn't hold back tears after she won. The father of her caddie, Greg Johnston, died a week ago and Kerr said she wanted to win it for both of them. It also was her first victory since becoming a mother at the end of 2013. Her son, Mason, was in a stroller behind the 18th green.
''I've been working with a new coach, and I definitely found something this week,'' Kerr said. ''He said I was going to have a hot round, and he was right. I just found something. I'm just real happy right now.''
Kerr had gone 42 LPGA starts without winning until Sunday at the Kia Classic.