Goals by Marcus Rashford in the ninth minute and Ferran Torres in the 18th at Camp Nou on Sunday gave Barcelona the victory and an insurmountable 14-point advantage over their fierce rivals with three rounds remaining in La Liga.
Barcelona coach Hansi Flick was in the dugout for Sunday's clasico following the death of his father, which Barcelona announced hours before the game. Players from both teams wore black armbands, and there was a moment of silence before kickoff.
A draw would also have been enough for the Catalan club to seal their third league title in four seasons.
Madrid, who remain the most successful club in the league with 36 trophies, are ending a second consecutive season without a major title.
Sunday's defeat at Barcelona capped an embarrassing week for Madrid, marked by altercations between players in training that led the club to fine Federico Valverde and Aurelien Tchouameni 500,000 euros ($A813,000) each.
Rashford opened the scoring for the hosts with a wonderfully taken free kick, curling the ball over the wall and into the top corner.
Torres extended the lead from inside the area after a flick from Dani Olmo.
Flick's father reportedly died overnight. The coach celebrated Barcelona's goals and looked emotional after the final whistle.
"I will never forget this day. It was a tough day for me. It starts with this (news that) my father passed away, but here, my team is fantastic," Flick said.
"I really love it, this is like a family and they gave everything today and I'm really proud. It's amazing, in this stadium, and also in the clasico against Real Madrid, to win La Liga."
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