Gulbis, ranked 46th, and a winner in Rome in 2010 over Roger Federer, saved two match points in the third set but finally lost when he sent a forehand wide to the massive relief of a dancing, celebrating Nadal.
The Spaniard now stands 6-0 against Gulbis as his bid for a seventh Rome title continues against compatriot David Ferrer, who advanced in a walkover over against Philipp Kohlschreiber who was suffering from vertigo.
Nadal was fresh from his Madrid title at the weekend, winning five titles from seven finals since returning to tennis after a seven-month knee injury absence.
Top seed Novak Djokovic played without ankle pain in a routine 6-1, 6-4 defeat of Alexandr Dolgopolov for a quarter-final place at the Rome Masters.
Djokovic dispatched Dolgopolov in an hour, with five aces and 13 winners in a contest which began 45 minutes late due to morning rain.
The two-time Rome champion will play Czech Tomas Berdych, a winner over South Africa's Kevin Anderson 7-5, 6-2, in the last eight.