Marcus Rashford and Ferran Torres struck in the first half to help Hansi Flick’s side clinch La Liga in consecutive years, while consigning Madrid to a trophyless season.
Barca moved an unassailable 14 points clear of second-place Los Blancos with three matches remaining.
This was only the second time the outcome of La Liga has been decided directly by the result of a Clasico, with record 36-time champions Real Madrid winning their first title in 1932 after a draw with Barca.
Madrid arrived at the match embroiled in chaos, after midfielder Fede Valverde was ruled out with a head injury following a training ground scuffle with team-mate Aurelien Tchouameni, who started.
Barca coach Flick received bad news before the game, with his father passing away, but took his place on the touchline regardless, to oversee his side’s comfortable triumph.
The German opted for the energetic Rashford, on loan from Manchester United, on the right wing in place of injured teenage star Lamine Yamal.
The Catalans, who only needed to avoid defeat, came out with their eyes firmly locked on the prize, racing into a two-goal lead inside 18 minutes.
Rashford opened the scoring with a superb free-kick, whipping the ball into the top left corner from a position 20 yards out, right of centre.
Torres doubled the hosts’ advantage at a jubilant Camp Nou, the 62,000-strong crowd enjoying the first Clasico back there since the stadium was reopened.
Dani Olmo produced a clever backheel to allow Torres to burst into the box and ram past Thibaut Courtois.
Gonzalo Garcia, playing in place of injured Madrid superstar Kylian Mbappe, prodded narrowly wide after racing in behind Barca’s high defensive line. (AFP)