Real Madrid can end a four-year wait for the Primera Liga trophy by clinching the title with a victory at Athletic Bilbao on Wednesday (Thursday AEDT) regardless of three-time defending champion Barcelona's result against Malaga.
Madrid is seven points clear of its top rival with three games to play, so even a Barcelona loss earlier in the day will award the Spanish leader its record 32nd domestic crown.
Madrid's record achievement - Barcelona is next closest with 21 trophies - comes with the team building on its record 112 goals scored in a season, Cristiano Ronaldo looking to establish a record scoring total in a season and coach Jose Mourinho set to become the first coach to win league titles in four different countries.
Mourinho has won league titles in Portugal with FC Porto, in England with Chelsea and Italy with Inter Milan, and now the Portuguese coach looks set to add a Spanish title to his resume.
"A team like Madrid cannot continue on any longer being a supporting act," goalkeeper Iker Casillas said as he eyed his fifth league title with Madrid but the first in four years that have been dominated by Barcelona.
"We're a little tired of it and it looks like it's over. All of our work over these months, even years, is finally bearing fruit."
Ronaldo scored his record 43rd goal in Sunday's (Monday AEDT) 3-0 victory over Sevilla only for Lionel Messi to match that total with his own brace in Barcelona's 7-0 win at Rayo Vallecano. Messi's overall goal tally on the season is 65 goals to Ronaldo 57.
Barcelona's last three games, starting against Malaga, will serve as preparation for next month's Copa del Rey final against Athletic, which will be coach Pep Guardiola's last game in charge before handing over the reins to assistant Tito Vilanova.
Barcelona responded to Guardiola's announcement of his departure by thrashing Rayo for its largest ever away victory, with the coach rotating his team and leaving out Andres Iniesta and Cesc Fabregas.
Alexis Sanchez is questionable against Malaga, which is tied on points with third-place Valencia in the chase to qualify for Champions League football next season.
Valencia hasn't had the best week after it lost to Malaga last weekend and failed to reach the Europa League final.
"Everything depends on ourselves," said under-pressure Valencia coach Unai Emery, whose club has been third nearly all season long. "If we take three points against Osasuna (on Thursday AEDT), third place is ours."
On Tuesday (Wednesday AEDT), Villarreal travels to Sporting Gijon knowing victory secures its place in the first division and condemns Sporting - and likely Zaragoza - to relegation.
Villarreal is four points ahead of Sporting and Zaragoza, which welcomes Levante on Wednesday (Thursday AEDT) with the Valencia club also chasing the final Champions League spot. Villarreal is only three points behind Malaga.
Atletico Madrid must beat Real Sociedad to stay in touch with Malaga, which it trails by six points, while Athletic will likely have no chance if it loses to Madrid with it already trailing fourth place by seven points.
In other matches, it's: Getafe v Racing Santander, Granada v Espanyol, Mallorca v Rayo Vallecano and Sevilla v Real Betis.
Real Sociedad continues to hold the edge in the battle for a top-four finish in the Primera Division after a 2-1 victory at Sevilla.