On 5 January 2012, Sevilla confirmed the signing of Reyes, who agreed to a contract until June 2015.
He played his first game three days later, starting in a 1–2 away loss against Rayo Vallecano, and scored his only goal of the season on 5 May, in a 5–2 win in the reverse fixture.
His first goals of the following campaign came on 18 November 2012, through a first-half brace in a 5–2 Seville derby rout of Real Betis – the opening goal came after eleven seconds.

Reyes scored twice in 12 Europa League matches as Sevilla won the tournament in 2013–14, including one in the second leg of their last-16 win over city rivals Betis.
On 27 May 2015, in the final of the following season's tournament, reportedly his final game for the club, he captained and assisted Carlos Bacca's first of two goals as the team came from behind to defeat FC Dnipro Dnipropetrovsk 3–2 in Warsaw.
However, he remained, starting as skipper in the ensuing Super Cup against Barcelona in Tbilisi and scoring once his side came from 1–4 down to take the game to extra time, but lose nonetheless.

Reyes netted twice as Sevilla advanced to the final of the Copa del Rey, including once in a 4–0 home win over Betis for the round of 16.
He missed the final weeks of competition after undergoing surgery to his appendix, and on 1 June 2016 it was announced the 32-year-old would be released upon the expiration of his contract.
On 5 January 2012, Sevilla confirmed the signing of Reyes, who agreed to a contract until June 2015. He played his first game three days later, starting in a 1–2 away loss against Rayo Vallecano, and scored his only goal of the season on 5 May, in a 5–2 win in the reverse fixture. His first goals of the following campaign came on 18 November 2012, through a first-half brace in a 5–2 Seville derby rout of Real Betis – the opening goal came after eleven seconds.
Reyes scored twice in 12 Europa League matches as Sevilla won the tournament in 2013–14, including one in the second leg of their last-16 win over city rivals Betis. On 27 May 2015, in the final of the following season's tournament, reportedly his final game for the club, he captained and assisted Carlos Bacca's first of two goals as the team came from behind to defeat FC Dnipro Dnipropetrovsk 3–2 in Warsaw. However, he remained, starting as skipper in the ensuing Super Cup against Barcelona in Tbilisi and scoring once his side came from 1–4 down to take the game to extra time, but lose nonetheless.
Reyes netted twice as Sevilla advanced to the final of the Copa del Rey, including once in a 4–0 home win over Betis for the round of 16. He missed the final weeks of competition after undergoing surgery to his appendix, and on 1 June 2016 it was announced the 32-year-old would be released upon the expiration of his contract.
José Antonio Reyes