The 24-year-old midfielder has failed to make the breakthrough in the Barca first team and is now to end a 12-year stay Camp Nou, joining his older brother, Giovani, at El Madrigon.
"Barcelona and Villarreal have agreed to terms for the player Jonathan dos Santos," read a statement on Barca's official website.
"The transfer fee, which is a combination of a fixed sum and variables, could reach €2 million [£1.6m], and Barcelona reserve the right to be involved in the possible future sale of the player."
The Mexico international made just nine appearances for the first team since his promotion from Barcelona B, with a cruciate ligament injury suffered during training in October 2013 having curtailed his development at the club.
Villarreal confirmed on their official website that the player has agreed a five-year deal and will complete his transfer after passing a medical.
Dos Santos is scheduled be officially presented as a Villarreal player at a press conference on Thursday.