Second-half goals from in-form striker Roberto Soldado, defender Marius Stankevicius and substitute Jordi Alba sealed victory for Unai Emery's side and lifted them to 63 points.
With six matches left, Valencia are nine points ahead of fourth-placed Villarreal who host Real Zaragoza on Monday.
Sevilla's bid for a berth in next season's Europa League suffered a setback when they lost 1-0 at relegation-threatened Getafe.
Getafe's Miku netted the only goal in the 76th minute at the Coliseum stadium on the outskirts of Madrid, firing home after the Sevilla defence failed to deal with a looping pass to the Venezuelan striker.
With only nine points separating ninth from 19th in a congested bottom half of the table, Getafe climbed to 12th on 37 points ahead of Sunday's games.
Malaga's Julio Baptista struck twice on his return from injury to help secure a 3-0 win at home to Real Mallorca that lifted them out of the relegation places into 17th.
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