On November 19, 2012, Mathis was traded to the Miami Marlins along with Adeiny Hechavarria, Henderson Álvarez, Yunel Escobar, Jake Marisnick, Anthony DeSclafani, and Justin Nicolino, in exchange for Mark Buehrle, Josh Johnson, José Reyes, John Buck, and Emilio Bonifacio.
Mathis was expected to serve as the back-up to Rob Brantly.

In his first spring training game with the Marlins on February 23, 2013, Mathis broke his collarbone on a foul tip hit by Matt Holliday.
He was the only catcher with major-league experience besides Brantly, and was expected to miss 6 weeks.
Mathis made his season debut on May 16, going 0–4 with 2 strikeouts.
On June 30, he hit a walk-off grand slam against Tyson Ross of the San Diego Padres to give Miami the win, 6–2.
On November 1, 2014, the Marlins exercised their $1.5 million 2015 option on Mathis.

On December 18, 2015, Mathis re-signed with the Marlins on a 1-year deal worth $1.5 million.
He hit his third career grand slam (first since 2013) in a June 14, 2016 game against the San Diego Padres.
On November 19, 2012, Mathis was traded to the Miami Marlins along with Adeiny Hechavarria, Henderson Álvarez, Yunel Escobar, Jake Marisnick, Anthony DeSclafani, and Justin Nicolino, in exchange for Mark Buehrle, Josh Johnson, José Reyes, John Buck, and Emilio Bonifacio. Mathis was expected to serve as the back-up to Rob Brantly.
In his first spring training game with the Marlins on February 23, 2013, Mathis broke his collarbone on a foul tip hit by Matt Holliday. He was the only catcher with major-league experience besides Brantly, and was expected to miss 6 weeks. Mathis made his season debut on May 16, going 0–4 with 2 strikeouts. On June 30, he hit a walk-off grand slam against Tyson Ross of the San Diego Padres to give Miami the win, 6–2. On November 1, 2014, the Marlins exercised their $1.5 million 2015 option on Mathis.
On December 18, 2015, Mathis re-signed with the Marlins on a 1-year deal worth $1.5 million. He hit his third career grand slam (first since 2013) in a June 14, 2016 game against the San Diego Padres.
Jeff Mathis