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The win took the east-coast club provisionally 18th after their previous two games had been postponed following the disaster at the end of October which killed 227 people.
Los Che coach Ruben Baraja said he hoped to turn the emotional nature of the match into positive energy for the team to try to bring the fans joy.
Emotions ran high before the game as a minute of silence was held as players stood before a huge Valencia region flag and tribute banner in the stands.
READ ALSO: Why is Spain’s Valencia region so prone to destructive flooding?
Defender Cesar Tarrega, who was in tears ahead of the match during the memorial to the flood victims, sent the hosts ahead after a scramble in the box following a short corner routine.
Hugo Duro’s own goal soon pulled Betis level but the forward made amends in the second half with two fine finishes to put Valencia two goals ahead.
Diego Lopez smashed in a superb fourth for Los Che and although Chimy Avila pulled one back for the visitors, Valencia were able to hold on to a morale-boosting victory.
MAPS: The other parts of Spain at risk of recurring flash floods