Molinari finished the tournament in style, not dropping a shot in his round and ending up at eight-under-par for the tournament to surge up the field at the Royal Golf Club in Seville.
Overnight leader Simon Dyson had a day to forget, with a four-over par round of 76 sending him in the other direction and into a share of 12th.
"Everything went according to the plan perfectly," Molinari said after taking his fifth career win.
"It's always special to win on tour, but to win in Spain in these circumstances is even better."
The tournament marked a year since the death of Spanish golfing legend Seve Ballesteros, and the champion’s memory loomed large over the event.
Two Spaniards, Pablo Larrazabal and Alejandro Canizares, were left in a tie for second, along with Soren Kjeldsen of Denmark.
But Molinari was the story of the day, with the four-shot deficit he overturned to win the biggest seen on the European Tour this season.
"It's not easy," the 29-year-old added. "I just tried to stay calm, hitting fairways, hitting the middle of the green. I was happy with the eight-under finish."
Despite the victory, his first in 18 months, Molinari remains outside the qualifying positions for this year's Ryder Cup.
"I just have to play the same golf a few more weeks and hopefully I will be there," he said.
"Everybody is desperate to make the team, but unfortunately for us there are only 12 spots.
"It's going to be hard - there are a lot of great players in Europe at the moment."