Unseeded Russian Samsonova beat Estonian Kanepi 4-6 6-3 6-3 to take the title in Washington on Sunday.
It was Kanepi, the tournament's sixth seed, who struck first in a tight opening set with strong serving from both players, capitalising on the only break point opportunity in the 10th game.
While Samsonova won at least 70 per cent of her service points in each of the three sets, Kanepi's effectiveness dipped after the opener, with a 77 per cent (20-of-26) success rate in the first set, which dropped to 63 per cent (15-of-24) in the second and the third (12-of-19) to provide the Russian with an avenue back into the contest.
Kanepi led 3-2 in the second set, before Samsonova rattled off the next five games, securing a double break in the process and forcing a decider.
In a tight third frame, with Samsonova leading 4-3, she created three break point opportunities and only needed the first to grab a winning buffer, serving out the match for the title.
It is the 23-year-old's first singles title since her maiden victory at the German Open 14 months ago, and she only dropped two sets in the process while defeating fifth seed Elise Mertens, second seed Emma Raducanu, China's Wang Xiyu and Australia's Ajla Tomljanovic.