Raul broke the deadlock early in the game before Arjen Robben doubled the lead midway through the first half.
Substitutes Gonzalo Higuain and Ruud van Nistelrooy were on the scoresheet in the second half to condemn Barcelona to a heavy defeat.
Thierry Henry scored a late consolation for Barcelona but his strike was not enough to alleviate the pain of such a humiliating defeat.
Barcelona's Dutch coach Frank Rijkaard, whose side ended a second successive season empty-handed, is expected to be sacked after a dismal term.
The defeat denied Barcelona an automatic Champions League place.
They will have to play in the qualifying phase after Villarreal ensured they will finish as runners-up following a 2-0 victory at relegation-threatened Recreativo Huelva.
Rijkaard surprisingly deployed youngster Bojan Krkic as a lone striker, supported by Henry and Lionel Messi on the flanks.
Henry was a peripheral figure in the first half, just like he has been since his arrival from Arsenal, where he used to excel as a striker.
On the other hand, Real coach Bernd Schuster opted not to include Van Nistelrooy and Robinho in his side's starting line-up.
Early Storm
Raul scored his 18th goal of the season after 13 minutes to put Real in front.
Guti robbed Rafael Marquez on the edge of the area and the ball slipped into the path of Raul, who curled a delightful left-footed shot past Victor Valdes.
The 30-year-old could have doubled the lead five minutes later after Valdes failed to deal with Fernando Gago's weak half-volley.
Raul approached to capitalize on the rebound but the Spanish guardian managed to handle the ball on the second attempt.
Robben extended the hosts' advantage in the 21st minute when he headed home Guti's in-swinging free kick.
In an attempt to revive an outplayed Barca side, Rijkaard introduced Giovani dos Santos instead of Icelandic forward Eidur Gudjohnsen, who played in the heart of midfield.
The substitution barely had an impact as Real maintained their complete domination at Santiago Bernabeu.
Barca's only chance in the first half came in the 26th minute when Henry's curling free kick went just wide of the post.
Misery Compounded
Argentinean forward Higuain added the third two minutes past the hour mark after some good work by Mahamadou Diarra down the right flank.
Diarra got the better of Yaya Toure and fed Higuain, who was totally unmarked inside the area. The former River Plate man coolly lifted the ball over Valdes and into the net.
Van Nistelrooy, who replaced fans' favorite Raul, completed the rout in the 77th minute from the spot after Robinho's shot struck Carles Puyol's hands.
Henry scored the Catalans' only goal four minutes from time when he latched onto Messi's deft pass to curl past Iker Casillas.
Barcelona ended with ten men on the field after Xavi Hernandez was sent off for picking up a second yellow.