Marcelino Garcia Toral's charges opened the scoring in the first half through a clinical counter-attack finished off by Rodrigo, before Simone Zaza broke his 14-game scoring drought early in the second half to hand the hosts a comfortable win on home soil.
Victory in the port city has now extended Valencia's unbeaten run in the league to five games and cemented the Bats as growing favourites to claim Champions League football come the end of the season.
Betis started the contest with purpose in attack, as Joaquin broke down the left to send the ball towards the back post for wing-back Antonio Barragan, who saw his first-time volley cannon into the body of Jeison Murillo.
Neither side were able to offer too much quality in the final third in the first half, but Daniel Parejo did come alive on the edge of the box to feed Goncalo Guedes, whose shot in frustration was calmly gathered by Antonio Adan in the Betis goal.
Guedes soon made up for his effort, though, as the winger played a crucial part in the opener, which Valencia bagged in the 23rd minute.
The Paris Saint-Germain loanee picked up possession just shy of his own box to send a long ball deep for the run of Rodrigo, who made a mockery of both Jordi Amat and Marc Bartra with some fine movement before sending a memorable finish beyond Adan to cap off a fine counter-attack.
Valencia gradually grew into the contest and they might have won a penalty before the break, only for the referee to wave play on despite Rodrigo going down under the challenge of Barragan when trying to meet a teasing cross from Carlos Soler.
The hosts were able to grab a crucial second just minutes into the second half, though, as first-half substitute Zaza was picked out by an adroitly chipped through-ball from Geoffrey Kondogbia, allowing the Italian to finish coolly under the body of Adan to end a scoring drought that had stretched back to December 2017.
Betis were able to offer little in the final third, but they almost found a route back into the contest through Joaquin, although Neto proved equal to the playmaker's free kick by getting down low to keep it out of his bottom corner.
Quique Setien's men might have been able to mount a late challenge, but they had a goal ruled out for a supposed foul from Loren on Neto 15 minutes from time, eventually allowing Valencia to see out a comfortable clean sheet as they furthered their credentials to mount a late challenge to sneak into the top three.
VALENCIA (4-4-2): Neto; Montoya, Paulista, Murillo, Gaya; Soler (Coquelin, 74'), Parejo, Kondogbia, Guedes; Santi Mina (Zaza, 37'), Rodrigo (Torres, 84')
REAL BETIS (3-5-2): Adan; Mandi, Bartra, Amat (Tello, 83'); Barragan (Guerrero, 59'), Garcia, Fabian, Junior, Camarasa (Castro, 69'); Loren, Joaquin