The 24-year-old was close to linking up with the Yellow Submarine last summer when he left Tottenham Hotspur, but he eventually opted for Mallorca.
However, following their relegation from La Liga and Villarreal's promotion to the top flight, the Mexican international has finally secured his switch.
"I am very happy to take this step in my career and, eventually, to play at Villarreal CF," he told the club's official website. "I hope I can contribute in any way I can. I am convinced that we will make a great season."
Dos Santos has signed a four-year contract at El Madrigal.