Marcelino Garcia Toral's men are already set for a UEFA Europa League spot next season, but they remain intent on avoiding qualification through the play-offs as they eye sixth place.
Ikechukwu Uche netted his 13th La Liga goal of the season in the 22nd minute, making him the division's highest-scoring African ahead of Granada's Youssef El Arabi.
Bruno Soriano doubled Villarreal's lead three minutes before the break as the hosts went into half-time on-course for another victory.
Jonathan Pereira gave the home side a three-goal lead nine minutes after half-time and Rayo's already-difficult task was made even harder in the 63rd minute as Anaitz Arbilla received a straight red for a tackle from behind on Moi Gomez.
Ten-man Levante defeated city rivals Valencia 2-0 at home in Saturday's late match.
Juan Antonio Pizzi's players were unable to oblige, however, and although the match was goalless for over an hour, Levante eventually broke through.
Andreas Ivanschitz added number two with 81 minutes on the clock and although Pedro Lopez's late red card initially put Levante's position in doubt, they held on to move up to eighth place with 48 points.
