The German club – second in the league and still in the Champions League – announced the deal on Thursday
The 27-year-old left-footer joins on a loan until the end of the season, with Leverkusen having an option to buy the former Atlas player after that.
“Andres Guardado is a very experienced player,” said Bayer 04 sporting director Rudi Voller in a statement on the club’s website, stressing the Mexican’s versatility. “He was a regular in Valencia and played in the Champions League last season.”
Added German legend Voller: “We are convinced that he will give our team a boost.”
Guardado, who has 99 caps for Mexico, declared himself delighted at the move.
“The offer from Leverkusen was a great opportunity for me to start something new,” he told the club’s website. “The Bundesliga has a fantastic reputation in Spain.”
Guardado could debut as early as Saturday, when Leverkusen takes on Stuttgart in the BayArena.
Valencia also announced that Dorlan Pabon and Helder Postiga have left the club. Pabon is headed to Sao Paulo while Postiga moves to Lazio.