The Golden Ball winner was the star of the show - again - as the Blaugrana all but clinch progression to the semi-finals of the Copa del Rey.
The 2010 FIFA Ballon d'Or winner produced a trio of neat finishes to overcome the resistance of the Seville side, and further strikes from Pedro and Seydou Keita meant that the Blaugrana will cruise into the last four.
Betis boss Pepe Mel said prior to kick-off that his team would play without fear and come to the Camp Nou to attack, and attack they did; they created more chances than the majority of sides who have travelled to Catalunya so far this season.
Attacking duo Jorge Molina and Ruben Castro were constantly on the move, with Molina in particular coming close to scoring. He had already struck wide of the target before he forced Pinto into a reaction save down.
Barca as expected inevitably created opportunities of their own. David Villa struck the post twice within the first half hour, the first an instant shot from Maxwell’s cut-back, the second a curling free-kick that visiting 'keeper Casto did well to glance onto the upright.
Messi, presented with the Ballon d’Or prior to kick off alongside team-mates Xavi and Andres Iniesta, gradually grew into the match. His excellent control and volley forced a point-blank block from Casto, but then on the stroke of half-time the world’s best player marked the occasion by opening the scoring.
Iniesta stroked the ball into his path on the right of the area, and as Casto advanced, he cutely lobbed the ball over his head and into the empty net.
But the Verdiblancos were just as much of a threat in the final third as the Spanish champions. Ruben Castro had smashed an effort against the crossbar in first-half injury time, and in the opening spell of the second half, he stung the gloves of Pinto with two powerful shots.
The Blaugrana were by no means at their best, but their efficiency in front of goal proved to be the difference, and once again Messi showed his class on the hour mark.
David Villa played the ball through, and as Casto approached he blocked the Argentine’s initial effort, but Messi had the presence of mind to get to the rebound and rolled the ball, somewhat fortuitously, through the goalkeeper's legs and into the far corner.
It was slightly harsh on Betis at that stage, but Mel’s side disintegrated after conceding the second, and Messi took full advantage, ensuring the home side dominated the rest of the proceedings.
The 23-year-old netted six hat-tricks in 2010, and duly added his first of 2011 by running clear of the back line, dummying Casto, and sliding the ball into the opposite corner. Thirty-one goals so far this season in all competitions - an astonishing return from the untouchable attacker.
Within minutes, it was four. Dani Alves was given the freedom of the pitch on the right, cut inside, and although Casto blocked the shot, the Brazilian rolled a pass to Pedro, who lashed the ball home.
Then it was five. Iniesta reached the byline and scooped a cheeky cross to the back post, met by substitute Seydou Keita, who nodded into the corner from underneath the crossbar. Betis looked shattered, and the second leg had became academic.
The Segunda Division side had requested that the first leg be played at their own stadium, because they felt if they suffered a heavy defeat at the Camp Nou, no-one would attend the return match.
Unfortunately for them, that is precisely what has happened - Barcelona are all but through, and the dream final versus Real Madrid remains a distinct possibility.