Both Barcelona and Real face opponents they should each comfortably beat at 5pm local time, with destiny in the hands of one-point leaders Barca.
The Catalan side needs a win against Granada to secure its 24th La Liga title. But a draw, combined with a win by Real against Deportivo la Coruna, would hand the Madrid team a record 33rd domestic crown.
The latter scenario is unlikely, however, as Granada have lost nearly half of their matches this season, and are on a -20 goal difference -- a stark contrast to Barca's +80. (Real Madrid are on a goal difference of +74.)
This will be the tenth time that Barca have glided into the final day of the season with destiny in its hands -- and it's sealed the deal in all nine of its previous attempts. A win would also ensure Barca's sixth title in its last 10 seasons.
Real have been on a hot streak themselves, winning 11 league matches in a row under manager Zinedine Zidane, who was appointed mid-season. The streak includes a 2-1 win at Barca on April 2 and a 7-1 home win against Celtavigo on March 5.
They have also qualified for the Champions League final, to be played at the end of the month against city rivals Atletico.
"We do still have faith, why not?" Zidane said at a news conference on Friday
. "We are just one point behind. We will believe in our chances until the final second.
"This is the game of our lives tomorrow, as we are playing for something very important. Then after this game we will have another to prepare for and win."
"We must start the game strongly," he added, referring to the matchup against Deportivo.
"It will be difficult as it is away from home. Depor are a good team, they know how to play football and their fans will want to end the season the best way possible. We must focus on what we have to do ourselves, from the first minute."
Barca hone in on title defense
Last weekend Barca hammered city rival Espanyol 5-0 to keep them ahead in a tight race that until recently included Atletico Madrid.
Barca started the day level on points with Atletico, but ahead in the standings thanks to a superior head-to-head and goal difference.
But Atletico's stunning 2-1 loss at already relegated Levante meant that it slipped back to third position behind city rival Real, which overcame Valencia 3-2 at the Santiago Bernabeu.
"We deserve the league title and I hope we can be precise in the final game to win," Barca boss Luis Enrique said after the match in comments carried by Barca's official Twitter account.