In July 2014, he was transferred to Liga MX club Tigres UANL to play the Apertura 2014 season. Guzmán made his official debut with Tigres in a 0–0 draw against Atlas de Guadalajara at the Estadio Jalisco on 19 July. That season, Guzmán and his club made it to the finals of Liga MX against Club América. In the home leg, Tigres won by 1–0 with goal of Joffre Guerrón. In the second leg, Guzmán received a red card, as did teammates Hernán Burbano and Damián Ariel Álvarez. Tigres lost 3–0, in an overall score of 3–1.[3]
In December 2015, Guzmán and his team became champions of the Apertura 2015 season. In the first leg of the finals against Pumas UNAM, Tigres won by 3–0. In the second leg, Pumas won by 3–0. In extra time Tigres scored the 1–3 at 103' but Pumas equalized 1–4 at 119'. After an aggregate of 4–4, Tigres won via penalty shoot-out 4–2, with Guzmán stopping the fourth shot from Pumas.
A year later, Guzmán and his team faced América to become champions for the fifth time. In the first and second leg the teams tied 1–1. After an aggregate of 2–2, Tigres won via penalty shoot-out by 3–0, with Guzmán stopping all 3 penalties. Guzmán was named MVP of the second leg and named best goalkeeper of the Apertura 2016, with 9 clean sheets and impressive saves against América in the finals.
In the second leg of the Round of 16 tie in the 2020 CONCACAF Champions League against Alianza, with his team on the verge of elimination due to the away goals rule since the score was tied on aggregate, Guzmán scored a header off a free kick in the fourth minute of second half added time to give his team the victory in the tie.[4]
In May 2018 he was named in Argentina's preliminary 35-man squad for the 2018 World Cup in Russia.[7] Guzmán was called up to the final 23-man squad after first-choice keeper Sergio Romero was ruled out through injury.[8]