More usually contenders for the competition's wooden spoon, Italy proved their victory over the French two seasons ago was no fluke as they defended well and took their chances against the 2011 World Cup runners-up.
Tries from captain Sergio Parisse and Martin Castrogiovanni, plus 10 points from man-of-the-match Luciano Orquera and three from substitute Kris Burton led them to victory, just their third ever over the French.
France were far from their best and despite tries from Louis Picamoles and Benjamin Fall and eight points from a rejuvenated Frederick Michalak, they were deservedly beaten by Jacques Brunel's effervescent side.
"I'm really happy for the team and the fans, after two years we've beaten France again in Rome," Orquera said.
"We were mentally extremely strong right from the beginning, we wanted to win at any cost and we were always in the match. We never gave up."
As the match moved to its close, France turned the screw, and with a minute left Davide Giazzon was sin-binned, leaving the home fans to suffer for the excruciating final seconds of last-ditch defending.
But with a huge crowd roaring their team on they kept their opponents at bay for an incredible win and a dream start to the Six Nations for their French coach Brunel against his countrymen.
"I was in emotional turmoil the whole match," Brunel said. "France are a great side and it's never an easy game. The match could have gone either way as we saw.
"The team has really grown and today they demonstrated their strength. It's the right time to manage Italy."
France manager Saint-Andre was left to reflect on where it had all gone wrong.
"We lacked precision and accuracy. We didn't take advantage of our chances while we were in the lead and the Italians overtook us," he said.
"The first half an hour was bad and the last half an hour was a catastrophe. It hurts but it's only one game. What we have to do now is concentrate on the Wales match on Saturday."