Roberto Soladao put the hosts ahead with a 16th-minute penalty, visiting defender Antonio Amaya dismissed for a goal-denying foul on the Spain striker.
Paulao's own-goal ended any hopes of a Betis comeback with five minutes remaining, the Brazilian defender turning Sergio Canales's cross past keeper Adrian.
Brazil striker Jonas added a third in stoppage time after arriving unmarked at the far post.
Valencia are holding down a spot in the Europa League in fifth place with a record of 13 wins, nine losses and six draws for 45 points.
Betis are in seventh place, and in striking distance of Malaga in sixth with a record of 13 wins, 11 losses and four draws leaving them one behind after 28 games.
Valencia were able to convert their 62.1% possession rate into a victory.
Los Che's ball control tactics produced 12 shots, including four on target, while also drawing 12 free kicks from fouls and nine corners.
They also completed 402 passes and had 33 crosses in the match.
The four attempts by Tino Costa were the most of any Valencia player.
Diego Alves made four saves for Los Murcielagos.
Daniel Parejo's 13 passes to Tino Costa were the most between any Valencia team-mates during the match.
Nelson Valdez was brought on to replace Soldado in the 52nd minute when the latter went down with an injury.
Los Verdiblancos had 37.9% of the possession during the match. Real Betis had nine shots, including four on target.Rubén Castro had three shots for Beticos, more than any of his team-mates.
The combination of Adrián to Jorge Molina was the most common during the match, as the two players connected 18 times.
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