Pérez career began in Deportivo Maipú, like his father, and started his professional playing career with Godoy Cruz, where he wrote his name into club history by scoring a fifth minute goal in the 1–1 draw with Belgrano on 9 September 2006. This was the first goal ever scored by Godoy Cruz in the Argentine first division. In total he has scored 12 goals in his career at Godoy Cruz, most of them on penalty shots. In 2007, Pérez joined Estudiantes de La Plata, where he finished as runner-up with the team in the 2008 Copa Sudamericana. He was then a first team regular in the team that won the 2009 Copa Libertadores.
On June 8, 2011, he has agreed a five-year contract with Benfica for a fee rumored to be around €5.5 million euros for 100% of his rights to Estudiantes de La Plata. After a serious knee injury sustained in the Champions League qualifiers, Pérez was loaned back to Estudiantes for six months on February 9, 2012.
On July 27, 2012, at the 2012 Eusébio Cup, he scored a long shot against Real Madrid from a very tight angle to complete the rout 5-2.
In 2012-13 season, Pérez was successfully converted into a central midfielder, partnering with Nemanja Matić, assuming a central role in commanding the team. His influence was further increased after the departure of Matic, being a vital part in league title campaign, and the second consecutive European final, although he was not present in it, after being sent off in the semi-final against Juventus on 1 May 2014. His performances attracted attention from other clubs, while Jorge Jesus named Pérez, the most difficult player to replace, and the 'brain' of the team. On 6 July 2014, he won Player of the Year for his performances.