He has played 89 matches for the Uruguay national football team, including the 2010 FIFA World Cup and the 2001, 2004, 2007 and 2011 editions of the Copa América.

During his time at Monaco he had to battle for his place in the defensive midfield spot against Lucas Bernardi, Akis Zikos and Gerard López and was especially favored by the manager Francesco Guidolin during the Italian's reign in the 2005–06 season.

[4][5] At Bologna, he has teamed up with fellow Uruguayan internationals, Henry Damián Giménez, Gastón Ramírez and Miguel Britos, before this left the squad to join S.S.C.

Pérez was capped for Uruguay in four successive editions of the Copa América, helping his country lift their 15th South American championship in 2011.

[9][10] Pérez was the assistant manager of the Uruguay under-20 team which won the 2023 FIFA U-20 World Cup and finished as runners-up at the 2023 South American U-20 Championship.