On 28 May 2012, Guardado signed a four-year contract with Valencia CF. He made his debut on 19 August, playing 66 minutes in a 1–1 away draw against Real Madrid; two days later, following his five-year residence in the country, he attained his Spanish citizenship. His maiden appearance in the UEFA Champions League took place on 12 September, in a 1–2 group stage loss at eventual winners FC Bayern Munich. During his first season he featured regularly at left-back, mainly due to the serious injury of Jérémy Mathieu.