Villarreal secured a return to the Champions League after four seasons away by beating Valencia 2-0 to sew up fourth place in La Liga.
Marcelino made a string of changes for the trip to Mestalla, due to the game falling between the two legs of Villarreal's Europa League semi-final against Liverpool, which the Yellow Submarine lead 1-0 ahead of a trip to Anfield next week.
Samu put Villarreal ahead with a fine finish after Roberto Soldado had opened up space inside the penalty area, before a reckless high line from Valencia allowed Adrian Lopez to run clear from his own half and follow up his midweek European heroics by dinking home.
The visitors held out comfortably in the second half and the final whistle was greeted by jubilant celebrations, with Marcelino's men now able to put all their energy into possible Europa League glory, having moved six points clear of fifth-placed Athletic Bilbao.
Crucially, Villarreal have taken four points from the Basque club this season to ensure the head-to-head advantage with two rounds of fixtures to play.
Athletic had beaten Celta Vigo 2-1 earlier on Sunday to leapfrog their opponents.
At the bottom of the table, Getafe boosted their chances of survival enormously by taking a 2-0 win from Deportivo La Coruna.
Pedro Leon and Carlos Vigaray got the goals at the Riazor to put Getafe on 35 points, level with Sporting Gijon, who won on Friday, and Rayo Vallecano after their loss at Atletico Madrid.
The teams from 16th to 19th are separated by a point heading into the final games of the campaign as the fight to stay up goes down to the wire.
Levante, six points adrift of Rayo and Getafe in the bottom three, will be facing relegation if they lose at Malaga on Monday.
In Sunday's other game, Sevilla's miserable campaign on the road dragged on as they lost 1-0 at Espanyol, whose victory vaults them onto 40 points, 14th place and clear of the scrap below them.