Despite Villarreal's bright start, Betis had the game’s first chance when Hector Bellerin's effort from the edge of the area was saved by Peter Gulacsi.
Shortly after, it was the hosts' turn to threaten as Gerard Moreno’s ball across from the left found Santi Comesana, whose close-range strike was expertly tipped onto the post by Real Betis goalkeeper Alvaro Valles.
Aiming to pick up their first victory under Inigo Perez since his summer appointment, the home side thought they had taken the lead as Carlos Romero's ball fell to Tajon Buchanan, allowing the Canada international to rifle past Valles, only for VAR to rule the goal out for offside in the build-up.
Nevertheless, El Submarino Amarillo continued to probe and were soon in front regardless when Renato Veiga's header across goal picked out Moreno six yards out, and the striker did the rest with around half an hour on the clock.
It was a notable contrast to the pre-match trend, with Betis having opened the scoring in seven of the previous eight H2Hs.
In response, Manuel Pellegrini's men looked dangerous and, within 10 minutes, they were back on level terms as, although Gulacsi saved Abde Ezzalzouli's effort, Cucho Hernandez was able to fire home the rebound.
The visitors then completed the turnaround just before half time when Natan fired into an empty net after Gulacsi had parried a deflected corner into his path.
Ezzalzouli was involved again early in the second half, picking out Hernandez inside the box, but Gulacsi was equal to his attempt.
Betis continued to push forward as they looked to establish a two-goal cushion and nearly found it when Hernandez broke clear, only to fire wide of the Hungarian’s right-hand post.
Despite the slender one-goal advantage, Betis never really looked like giving up their advantage, underlining the issues Villarreal continue to have since Perez replaced Marcelino in the dugout.
Such has been their drop in form, they are now in the relegation zone, having qualified for the UEFA Champions League last term. Meanwhile, Betis climb to third with 12 points (W4, L1), having won five of their six games in all competitions as they go from strength to strength.
Flashscore Man of the Match: Peter Gulacsi (Villarreal)