The headline names will start in their respective attacks as the Azzurri celebrate their country's 150th birthday by hosting Oscar Tabarez's side in Rome
Christian Maggio, Federico Balzaretti and Pablo Daniel Osvaldo come in for Ignazio Abate, Domenico Criscito and Giampaolo Pazzini, with the Azzurri lining up in their familiar 4-3-1-2 system.
The Copa America winners start with Edinson Cavani and Sebastian Fernandez leading the line in the absence of the injured Luis Suarez and Diego Forlan.
Midfielder Nicolas Lodeiro is also among Oscar Tabarez's absentees for the game, which kicks off at 20.45CET.
Italy (4-3-1-2): Buffon; Maggio, Ranocchia, Chiellini, Balzaretti; De Rossi, Pirlo, Marchisio; Montolivo; Balotelli, Osvaldo.
Subs: De Sanctis, Sirigu, Abate, Ogbonna, Aquilani, Thiago Motta, Nocerino, Matri, Pazzini, Pepe.
Uruguay (4-4-2): Muslera; Caceres, Lugano, Godin, A. Pereira; M. Pereira, Perez, A. Rios, C. Rodriguez; Fernandez, Cavani.
Subs: Silva, Scotti, Coates, Eguren, Ramirez, D. Rodriguez, Gonzalez.