كتب : وكالات
The Argentina wizard broke the deadlock when he connected from point-blank range with a low cross whipped in by substitute Ibrahim Afellay 14 minutes from time.
The evergreen Messi completed the rout on 87 minutes when one of his trademark sprints saw him elude three challengers to go one-on-one with Iker Casillas and hit a sensational strike.
Barcelona were reduced to ten men after temperamental goalie Jose Manuel Pinto received his marching orders for launching into a fight with a member of Real's coaching staff in a halftime rift.
But Real didn't have enough time to capitalize on their numerical advantage as defender Pepe was dismissed too for a harsh challenge on Daniel Alves one minute past the hour mark.
Barcelona seem poised for a Champions League final spot as the second leg takes place at Nou Camp next week.
Spanish titans Barca and Real locked horns twice this month before their Champions League encounter.
They played out a 1-1 draw on 17 April in a La Liga game before Los Merengues won the Copa del Rey upon beating their arch-rivals 1-0 in extra time four days later.
Manchester United defeated Germany's Schalke 2-0 in the Champions League semi-finals on Tuesday.
United and Barcelona are widely expected to face off in the final.
The Spanish giants were crowned European champions in 2009 after sinking the Red Devils 2-0.