With two games to play, Santander, one of the founders of the Spanish league, lead the second division by seven points and are assured of finishing in one of the two automatic promotion places.
Deportivo La Coruna, playing on Monday, could still beat Santander to the title but third-placed Almeria, who conceded two goals in the last 12 minutes to lose 2-1 at home to Las Palmas, cannot catch up.
Santander last played in La Liga in 2011-12, when they finished bottom of the table. They slid into the third tier at the end of the following season.
Last season, they finished fifth in Liga 2 but were eliminated in the playoff semi-finals.