The Spaniard edged South Africa's Garth Mulroy by two strokes while Italy's Matteo Manassero finished in a tie for third place with Frenchman Gregory Bourdy.
European Ryder Cup players Nicolas Colsaerts and Martin Kaymer also fared well with under two weeks to go until the match at Medinah.
The victory was the sixth European Tour win of Fernandez-Castano's career and his second on Italian soil - after his 2007 triumph in the same event.
The 31-year-old from Madrid had not won since last year's Singapore Open but held his nerve when he hit a solid shot out of the rough following an errant tee shot to birdie the final hole of the Royal Park I Roveri course.
Mulroy fell behind after a bogey on the 17th.
Colsaerts and Kaymer finished in a tie for fifth with Gary Boyd of England and Pablo Larrazabal of Spain, six shots back.