On 2 April 2006, Sanchez left temporarily to play with the Mexico national team for the 2006 FIFA World Cup in Germany, leaving Talavera in goal. Since then he has started six Clausura 2006 games for Guadalajara. In the first game he started the club posted a 2–0 loss against Monarcas Morelia. This was followed by a loss to Atlas in the Clásico Tapatío. In the final game of the season, Guadalajara lost to Toluca, 2–0, but after a terrible performance in the first leg of the quarter-finals against Jaguares when he made a big mistake in injury time that caused the winning goal for Jaguares, coach José Manuel de la Torre dropped him as the starter and was replaced by Luis Ernesto Michel and Guadalajara fought back and advanced to the semifinals. The next season, when Oswaldo Sánchez returned, Talavera saw himself as the third goalkeeper of Guadalajara, with Michel as the second keeper, after Oswaldo left Guadalajara, Michel was the starting keeper and Talavera the backup. After this, he didn’t have any action with Guadalajara again, taking the decision to leave the club in order to have more minutes played.

Guadalajara loaned Talavera to Tigres UANL on a one-year loan in 2008, in which he rarely saw action with the team, as he was competing with Óscar Pérez for the spot. Nevertheless, bad luck came for Talavera, as Talavera injured himself in training, making Enrique Palos the next in the line. After he had fully recovered, Alfredo was released from Tigres.

Talavera was transferred to Toluca as a substitute for first team goalkeeper Hernan Cristante, since he was injured for the Apertura 2009. On 26 July 2009, he made his league debut with Toluca playing against his former club Guadalajara in a 4–3 victory. He played as a starter in every game of the season as the team reached the championship semi-finals, losing to eventual championship winners Monterrey.

On 15 May 2010, Talavera made it to his first final as starter after defeating Pachuca 1–0 in the second leg of the 2010 Bicentenario championship semi-final (3–2 on aggregate). On 23 May, Talavera helped Toluca win the championship, defeating Santos Laguna in a penalty shoot-out 4–3 after stopping Fernando Arce’s shot. His performances led him to win the tournament’s Golden Glove award.

In January 2011, Talavera received his first call-up to the Mexico national team by José Manuel de la Torre for a friendly match against Bosnia and Herzegovina. He made his international team debut on 26 March 2011 in a friendly against Paraguay which El Tri won 3–1. He was called for the team’s 2011 CONCACAF Gold Cup squad as a third choice goalkeeper after José de Jesús Corona and Guillermo Ochoa. Following Corona’s Liguilla scandal with Cruz Azul and Ochoa’s clenbuterol issue, Talavera became Mexico’s first-choice goalkeeper, despite having only one international cap. Overall, he saw action in five matches of that tournament and was a starter in the final against United States, where Mexico would go on to win 4–2.

On 15 September 2013, in a league match against Puebla, Talavera scored a last-minute penalty, helping his team tie the match at 1–1, thus giving him his first goal in the Liga MX.

Talavera was named in the 23-man squad participating in the 2013 FIFA Confederations Cup held in Brazil, but did not appear in any of the group stage matches as Mexico failed to progress from the group stage. Following the conclusion of the tournament, Talavera was called up again to participate at the Gold Cup to replace injured goalkeeper Cirilo Saucedo.

On 2 June 2014, Talavera was included by Miguel Herrera to be in Mexico’s 23-man squad for the 2014 FIFA World Cup in Brazil, but did not appear.

Talavera was included in the final roster that would participate at the 2015 Copa América, but made no appearances. With the arrival of then-manager Juan Carlos Osorio in October 2015, Talavera became Mexico’s first-choice goalkeeper in various instances.

In May 2016, Talavera was included in the final roster to participate at the Copa América Centenario, making a single appearance in the opening group stage match against Uruguay, where Mexico won 3–1. On 7 July, Talavera was named in Mexico’s 18-man squad that would participate in the Summer Olympics in Rio de Janeiro, Brazil, being one of the three over-aged players. Playing as Mexico’s starting goalkeeper in the tournament, he was named captain following Oribe Peralta’s injury. Mexico failed to make it past the group stage.

In May 2018 he was named in Mexico’s preliminary 28-man squad for the 2018 FIFA World Cup in Russia, and in June 2018, he was named in Mexico’s 23-man squad for the 2018 FIFA World Cup, but did not receive any minutes on the field during the tournament.

Prior to the start of the 2020–21 season, Talavera joined Club Universidad Nacional in an exchange that saw Alfredo Saldívar join Toluca. On 26 July 2020, he made his league debut for Pumas U.N.A.M. in a 3–2 victory over Querétaro.