Espanyol took advantage of Jose Mourinho resting a host of first-team players in the first half ahead of Real's Copa del Rey final with Atletico Madrid on Friday.
And they deservedly went in front through Christian Stuani on 22 minutes.
However, after the introduction of Cristiano Ronaldo in the second-half, Madrid rallied and were level when Gonzalo Higuain flicked home Luka Modric's free-kick just before the hour mark.
But Los Blancos could not find the winner they needed to keep the title race alive as the point leaves them seven adrift of Barca with just two games remaining.
"There is nothing more to do than congratulate them," Real midfield Xabi Alonso told Canal Plus. "The league is a tournament of consistency and we had a very bad start that didn't allow us to compete until the end.
"Right now the objective of Real Madrid is the cup. We want to fight for this title because we have a great desire to lift it in our stadium."
Barca, who face Atletico Madrid on Sunday, could match Real's league record total of 100 points from last year if they win their remaining four games.
An incredible first-half to the season, in which the Catalans dropped only two from a possible 57 points, was the key as Barca virtually guaranteed the title in Tito Vilanova's first season in charge.
By contrast, Madrid were left to rue early season defeats at Getafe, Sevilla and Real Betis as they fell 18 points behind their rivals by the turn of the year.
And despite a difficult spell on and off the pitch in 2013 as Vilanova had to travel to New York for cancer treatment, Barca have remained consistent in the league thanks to another sterling season from Lionel Messi. The Argentine has scored in 20 consecutive league games he has been involved in and is just four shy of his own league record of 50 goals in a season.
The title win will no doubt be a balm for the Barcelona players following their Champions League exit last month, which included being blanked in both their semi-final legs against Bayern Munich (see picture gallery).
"This triumph is very special, a prize of effort, of an overcoming spirit and the perseverance of an extraordinary group of human beings," Barca president Sandro Rosell said via his Twitter account.
Real suffered a big blow ahead of the cup final early on Saturday when Raphael Varane limped off with a knee injury after just 18 minutes.
The visitors were still regrouping when they went behind shortly afterwards as a corner to the back post was prodded across goal by Sergio Garcia and turned in by Stuani.
The Uruguayan should have had a second five minutes later when he was released clean through on goal by Joan Verdu, but this time he hit the ball straight at the advancing Lopez.
Espanyol thought they had doubled their advantage seconds later when Hector Moreno headed home another corner from the right but he was adjudged to have pushed Xabi Alonso to gain leverage in his leap.
Mourinho introduced Karim Benzema at half-time and then Ronaldo 10 minutes after the break in an attempt to give Madrid more attacking thrust.
And after Ronaldo had been fouled two minutes later Higuain flicked in Modric's free-kick to level.
Ronaldo then fired into Kiko Casilla's arms on the volley from a narrow angle as Madrid looked the turn the match on its head.
However, the game was marred by petty tussles and a flurry of bookings in the second period as referee Ignacio Iglesias Villanueva produced 10 yellow cards.
And tempers flared again in stoppage time when Victor Sanchez dived in on Higuain and was shown a straight red card.
Madrid though couldn't make their man advantage count in the final seconds as Ronaldo skied a free-kick from 25 yards high into the stands.
Earlier Osasuna took a huge step towards securing survival as Alejandro Arribas' late goal gave them a 1-0 win over Getafe.
Los Rojillos are now four points clear of Deportivo la Coruna in the final relegation spot after they were beaten 1-0 at Valladolid.
And Mallorca remain rooted to the foot of the table after they went down 2-1 at Athletic Bilbao.
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