Coach Kieran Crowley has moved Ange Capuozzo from wing to fullback and Tommaso Allan returns to flyhalf, with Pani, making his World Cup debut, coming in on the wing to face a Uruguay side which impressed in their 27-12 loss against France.
Italy start with two sets of brothers for the first time in a World Cup game, the Garbisi and Cannone siblings all making the team.
Alessandro Garbisi takes over from Stephen Varney at scrumhalf while his brother Paolo wears the number 12 shirt for the first time, moving from flyhalf to replace Luca Morisi as centre.
Niccolo Cannone replaces lock Dino Lamb, who scored a try against Namibia and drops to the bench for this game. Lorenzo Cannone retains the number eight position.
Prop Riccioni comes in for Simone Ferrari, who is not in the match-day 23, while back row Sebastian Negri retains his place to make his 50th appearance for Italy.
Having won as expected against Namibia, and with New Zealand and France still to come, Italy can't afford to take the game with Uruguay lightly.
"We worked well during the week in Bourgoin," Crowley said. "We are in a World Cup, every game has its importance, its difficulties and its history.
"The preparation for the match against Uruguay was good. We will be focused on our performance."
Italy's last game against Uruguay gave Crowley his first win as coach of the Azzurri. In November, 2021, in his third game in charge, Italy won 17-10 against the South Americans.
Seven players from that Italian team will start against Uruguay, Ignacio Brex, Monty Ioane, Paolo Garbisi, Federico Ruzza, Danilo Fischetti, Negri, and captain Michele Lamaro.
Hosts France, New Zealand and Namibia are the other teams in Pool A.
Italy team: 15-Ange Capuozzo, 14-Lorenzo Pani, 13-Juan Ignacio Brex, 12-Paolo Garbisi, 11-Montanna Ioane, 10-Tommaso Allan, 9-Alessandro Garbisi, 8-Lorenzo Cannone, 7-Michele Lamaro (captain), 6-Sebastian Negri, 5-Federico Ruzza, 4-Niccolo Cannone, 3-Marco Riccioni, 2-Giacomo Nicotera, 1-Danilo Fischetti
Replacements: 16-Luca Bigi, 17-Federico Zani, 18-Pietro Ceccarelli, 19-Dino Lamb, 20-Manuel Zuliani, 21-Giovanni Pettinelli, 22-Alessandro Fusco, 23-Paolo Odogwu.