Rodríguez made his debut with the Mexico national team on 18 February 2004 in a friendly against Chile in Carson, California. He scored his first goal for Mexico on 8 July 2005 in a 1–2 CONCACAF Gold Cup loss against South Africa.

On 2 April 2006, he was called up by coach Ricardo La Volpe for the 2006 FIFA World Cup. Rodríguez played in the match against Portugal.

On 9 May 2008, it was announced that he was transferred for US$1.8 million to Dutch club PSV Eindhoven, the second Mexican in the latter squad with Carlos Salcido. Rodríguez was predominately during that debut season mostly on the bench, and proved an alternate centre backs for Dirk Marcellis. He scored his first goal with the Dutch giants on 25 November 2008 with a 30-yard shot against Heracles Almelo.

Prior to the start of the 2009–10 season, Rodríguez was given the number four jersey, previously worn by Manuel da Costa, who had transferred to Fiorentina in January 2008. He won a starting spot in the center of defence for both the Eredevisie and the Europa League.

Rodríguez was a part of the Mexico squad in the 2010 FIFA World Cup in South Africa. He was a starter in all of Mexico’s group matches, and played the Round of 16 match against Argentina.

On 14 July 2011, Rodríguez signed a three-year contract with VfB Stuttgart for an undisclosed fee. Rodríguez made his Bundesliga debut on 6 August 2011 in a 3–0 win against Schalke 04. He registered an assist in the 37th minute to Cacau, which gave Stuttgart a 2–0 lead in their 3–0 victory.

During the 2011 CONCACAF Gold Cup, Rodríguez, and four other members of the Mexico national team, tested positive for the banned substance of Clenbuterol and were withdrawn from the tournament squad. However, all players were exonerated as FIFA determined that the accused had ingested the banned substance via contaminated meat that had been served during a pre-tournament training camp. However, World Anti-Doping Agency appealed to the Court of Arbitration for Sport to request a ban. But on 12 October 2011, WADA withdrew this request after the full file was made available to them.

During the Apertura 2006, Rodríguez had a pivotal role in Guadalajara’s championship run, winning the final second-leg match 2–1 (3–2 on aggregate) against Toluca on 10 December. The win gave Chivas their eleventh league championship, a record which stood until América matched the achievement in 2013.

On 2 January 2013, Rodríguez was transferred to América. When América defeated Cruz Azul in the Clausura 2013 final, he became the first player in history to win a league championship with both América and Chivas, archrivals in Mexico’s biggest rivalry, El Súper Clásico. He had previously won the league title with Chivas in the Apertura 2006.

On 4 June 2014, Rodríguez was transferred to Cruz Azul.