Villarreal secured their safety in La Liga thanks to a 3-2 win at Sporting Gijon on Tuesday, while Granada also won.
Miguel Angel Lotina's side - who came fourth last term and have not finished outside the top eight since the 2002/03 campaign - have struggled this season thanks to a lengthy injury list and the departures of key players Santi Cazorla and Joan Capdevila.
But they finally made sure that they would avoid relegation at Estadio Municipal El Molinon with a gutsy away win against their fellow strugglers.
Mario bagged a 19th-minute opener for Villarreal and although Lora responded for Sporting Gijon, the visitors reclaimed the lead just before the break.
Marcos Senna was the scorer, netting a 43rd-minute penalty to give Lotina's men a lift before half-time.
And when Paraguayan Hernan Perez scored just 11 minutes into the second half, Villarreal's win looked safe.
Sporting gave them a late scare when Galvez pulled a goal back with five minutes left, but the visitors, who were reduced to 10 men with the 90th-minute dismissal of Cesar, held on for all three points.
Also on Tuesday, a first-half double to Nigerian Odion Ighalo helped Granada record a 2-1 home win against Espanyol.
Ighalo's goals on 29 and 35 minutes gave Abel Resino's side a healthy lead at half-time.
And despite Didac Vila's strike nine minutes into the second half, promoted Granada won to move up to 15th place on the table.
The day's other match saw Getafe and Racing Santander play out a 1-1 draw.
Senegalese midfielder Papakouli Diop missed a first-half penalty for Racing and they were made to pay when Venezuelan Nicolas Fedor netted a penalty of his own on 59 minutes to give Getafe the lead.
Diop quickly hit back with a goal to make amends for his early error, and his effort ensured both sides would share the spoils.
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