Marcelino's side headed into the match hoping to keep their unbeaten record this season intact and they received the perfect start when French forward Jeremy Perbet scored inside the first minute.
Substitute Jonathan Pereira doubled Villarreal's lead 23 minutes from time to spark celebrations in Estadio El Madrigal in the club's 500th Spanish top-flight fixture.
Although Sergio Garcia scored a late consolation for the losers, it could not stop the party as Villarreal's impressive start to the season continued.
Athletic Bilbao scored twice in the last 20 minutes as they came from behind to defeat Real Betis 2-1.
After a goalless first half, Benat missed a penalty in the 59th minute for Bilbao, and they were made to pay almost immediately.
Jorge Molina was the man responsible, firing Real Betis ahead after he followed up his initial headed effort which was well saved.
But Athletic drew level thanks to Oscar De Marcos' header, before Mikel San Jose scored the winner with eight minutes remaining.
San Jose rose highest to meet Ibai Gomez's cross with a thumping header as Athletic's 100 per cent home record at their new Estadio San Mames home continued.
Thursday's other game saw Getafe beat Celta Vigo 2-0 thanks to goals from Lisandro Lopez and Alvaro Arroyo, moving the Madrid side above their opponents and into 10th.
