Villarreal needed victory at the Sanchez Pizjuan stadium but saw its hopes deflated from the 10th minute following Renato's opener.
Villarreal created opportunities but the holders put the outcome beyond doubt with goals from Frederic Kanoute and Alexis Ruano within five minutes of the restart.
Sevilla plays either Real Madrid or Atletico Madrid next, with Madrid leading 3-1 after the first leg going into Thursday's match at the Vicente Calderon stadium.
Sevilla defender Sergio Sanchez returned to action for the first time since undergoing heart surgery to correct a condition that sidelined the 24-year-old defender a year ago.
