Appearing in his first Masters final, the 15th seed struggled to match Nadal, who needed just half an hour to wrap up the first set, winning more than double the points of his opponent.
Ramos-Vinolas settled down in the early stages of the second set, but at 2-2 he got broken for a third time with a mistimed backhand that sailed long.
Nadal experienced a brief wobble when leading 4-3, dropping to 0-30, but he pulled it back as Ramos-Vinolas buckled under tremendous pressure from his more illustrious opponent.
Having saved two championship points, courtesy of Nadal errors, Ramos-Vinolas then hit a double fault on Nadal's third championship point to confirm victory for the fourth seed.
As well as being his 10th title in Monte Carlo, Nadal's first trophy of the year is his 50th title on clay, taking him clear of Guillermo Vilas as the most successful man on the surface.