The young Italian fired a 4-under 67 at Club de Campo del Mediterraneo in Spain, finishing with a 16-under-par 268, four shots better than Ignacio Garrido.
The turning point in the final round came at the 15th, when Manassero passed third-round leader Gary Boyd. The teen converted his third straight birdie from 16 feet out to get to 16-under.
At the age of 17 years and 188 days, Manassero bypassed Danny Lee as the youngest European champion. Lee won as an amateur at the age of 18 years, 213 days.
Garrido posted a three-under 68 to take second place at minus-12 and Boyd (74) shared third place with Peter Lawrie (70), Christian Nilsson (72) and Joost Luiten (68) at 11-under-par 273.