At the age of 19, Pérez joined one of the clubs of his hometown, Defensor Sporting, soon becoming a first-team regular. He joined a larger club from Montevideo, CA Peñarol, in 2003 but only played 13 games with them before being shipped off to play for Didier Deschamps' AS Monaco. During his time at Monaco he has 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.
On 31 August 2010 he was signed by Italian Serie A team Bologna for €2.1 million (including 5% solidarity contribution to youth clubs). No fee was scheduled to pay on that day, but 2 equal installments was scheduled on 31 December 2010 and 30 June 2011. 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. Napoli. In Pérez first season in the Serie A, Bologna managed 16th place and finished six points clear of relegation, confirming a fourth successive season in the Italian top flight. He also managed three assists during the campaign, tied for most on the team along with Riccardo Meggiorini.
After without a club for 1½ months, Pérez signed a new 2-year contract with Bologna in August 2013.
Pérez has been capped for Uruguay in four successive editions of the Copa América, helping his country lift their 15th South American championship in 2011. He was also selected to 2010 FIFA World Cup. On 16 July 2011 he scored his first goal for the national team in a match against hosts Argentina in the Copa America quarterfinals, although he was also sent off in the same match. Pérez was back for the final match against Paraguay, starting in defensive midfield in a 3–0 win.