Nadal took his third clay-court title of the year with a 7-5, 6-3 decision over the top-ranked Serb.
The Spaniard's victory came six days before the French Open, the second major of the year, which Nadal also has won six times.
Nadal did not drop a set in the Rome event.
He also won Monte Carlo and Barcelona tournaments on clay this year.
Nadal has 49 titles in his ATP career. Thirty-five of them have been on clay surfaces.