The 20-year-old, ranked 101st in the world, is expected to soar nearly 50 places in the ATP standings after humbling fifth seed Ramos-Vinolas.
Playing in his third ATP final, Ramos-Vinolas converted his only break point in the opening set and looked poised to surge through the set but Khachanov forced a tiebreak before surrendering it 7-4.
However, Khachanov levelled the match against the Spaniard when he bagged a tightly contested second set 7-3 in the tiebreak.
Khachanov, who had beaten three seeded players en route to his first ATP final, relied on his strong service game, including 14 aces in the match, to complete a memorable win.
"I can't believe I won my first title," said Khachanov.
"At this level, all the players are really tough.
"I was playing against a guy much higher-ranked than me, so I just had to focus on every goal and keep going. You cannot lose focus and be relaxed.
"I was just pushing myself to the limit and I got the second set and then the third."
The Moscow native is the ninth first-time winner on the ATP tour in 2016.
