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De Rossi, captain on the night, converted a late penalty for the Azzurri to confirm victory - and to continue a remarkable personal scoring streak which saw him score four goals for Roma in the final five games of the campaign.
The 33-year-old won his 113th cap in the process, moving clear of Dino Zoff and into fifth on his own in Italy's list of all-time leading appearance makers.
Italy took the lead early on after an own goal from Uruguay defender Jose Maria Gimenez, before Inter Milan forward Eder scored with just under 10 minutes remaining to effectively seal the game.
De Rossi's Roma teammate Stephan El Shaarawy also played in the game, and was subsequently voted the man of the match.
De Rossi, El Shaarawy and the Azzurri are next in action against Liechtenstein in a World Cup qualifier on Sunday.
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