The unseeded 26-year-old played composed tennis throughout against the German, four years her junior, winning the match in just under 84 minutes.
Vesnina had lost six previous finals, three in 2011 alone, and sank to her knees in relief when a Barthel backhand sailed wide of the tram lines to give her a first title.
"I feel such a relief and I just want to cry honestly," Vesnina said. "I'm so happy that I won the final and I think in general I was pretty good.
"I didn't pressure myself at all I just went onto court and was thinking that 'this is my time, I have to do it and if I get a chance I have to use that chance'."
She meets France's Caroline Garcia in the first round of the Australian Open in Melbourne, while Barthel meets Ksenia Pervak of Kazakhstan.