Vesnina had appeared in six title matches since January 2009 but managed to win just one set before Saturday's breakthrough. Last year, Barthel picked up her first WTA championship at the Moorilla. That had been her only other finals appearance.
Vesnina, unseeded in the tournament, defeated fourth-seeded Yaroslava Shvedova and No. 2-seed Sloane Stephens in getting to the final against Barthel, the No. 9 seed.
Vesnina won five consecutive games at one point, going from 2-3 in the first set to taking the set and jumping ahead 1-0 in the second. She ended up with five breaks that offset the two games she dropped serve. Vesnina won 60 percent of the points on serve and 50 percent off Barthel's serve.
"I feel such relief right now. Honestly I just want to cry," Vesnina said. "I was a little nervous before the final but in general I felt good during the match. I just told myself, 'This is my time -- I just have to do it and if I get a chance, take it.'
"I didn't feel any pressure. I enjoyed all the other finals I've been in, I just lost to really good players. But it finally worked out for me. I've been waiting for this for a long time."
Vesnina's first-place check was for $40,000 and Barthel received $20,000 for finishing second.