"Despite his youth, Andres Guardado already has the experience of playing in two World Cups and ... is one of the mainstays of the Mexico team," Valencia sporting director Braulio Vazquez said on the club's website (www.valenciacf.com).
"We are talking about a player of great technical ability and international stature," he added.
Guardado has just helped Depor, whom he joined in 2007, win promotion back to Spain's top flight after one season in the second division.
He has 77 Mexico caps, scoring 13 goals, and played at the World Cups in Germany in 2006 and South Africa two years ago.
The 25-year-old said he was excited at the prospect of playing for Valencia, who finished third in La Liga last season, in the Champions League.
"Ever since I was a boy I watched the Spanish league and the Champions League on TV and I always dreamed of making it there one day," he said.