Vesnina had never advanced beyond the third round in singles, and just last year she lost in the first round of qualifying, though she has won three doubles titles at the desert tournament. She beat No. 2 seed Angelique Kerber and No. 12 Venus Williams on her way to the biggest final of her career at age 30.
Kuznetsova is 0-3 in finals here, also finishing runner-up in 2007 and 2008.
At age 31, Kuznetsova was the fifth-oldest women to reach the final. The two-time major champion struggled while playing with the lead as the No. 8 seed.
Kuznetsova led 4-2 in the third before 14th-seeded Vesnina broke her twice in sweeping the final four games of the match.
Kuznetsova served one of her nine aces to lead 4-1 in the second, and that prompted Vesnina to bring out her coach/father, Sergey Vesnin, for a chat.
Vesnina reeled off four straight games to lead 5-4. Her forehand error led to Kuznetsova's break in the 10th game that tied it 5-all. Vesnina broke back and served out the set 7-5.
Kuznetsova had luck on her side early, winning the first set on a net cord in the tiebreaker. She gave the traditional wave, acknowledging her good fortune to Vesnina, who had blown leads of 2-0 and 4-2.
Vesnina had 46 winners and 49 unforced errors. She successfully gambled at the net, winning 24 of 32 points during the three-hour match.
Vesnina earned $1,175,505 for her third career singles title and will move up two spots to a career-high No. 13 in the world rankings on Monday.