The Argentine etched his name in football history with his 85th and 86th goals for club and country in 2012, breaking the 40-year-old record of 85 set by Gerd Muller in 1972, while he also surpassed Cesar Rodriguez as the all-time highest league goalscorer for the Blaugrana with his 192nd Liga goal.
Messi's brace put Barcelona two goals up after 25 minutes, but it was far from plain sailing for the Catalans, who were given a thorough examination by a spirited home side that pulled a goal back through Ruben Castro shortly before the break.
The attacking pressure from Betis saw them create a number of opportunities in the second-half, hitting the woodwork twice, but Barca managed to ride their luck and grind out the victory, which gives them their 14th win in 15 league games, and restores their six-point lead over Atletico Madrid at the top of the table.
Messi shook off a knee injury sustained during the 0-0 draw against Benfica in midweek to start in a much-changed side from Tito Villanova, who retained only two players from his XI against the Portuguese outfit.
Betis fired an early warning shot with just over two minutes on the clock, after Joel Campbell picked out Salva Sevilla inside the area, but his header was placed too close to Victor Valdes.
Barca were handed a blow after 10 minutes as Cesc Fabregas, who appeared to be struggling, was withdrawn, with Alexis Sanchez coming on in his place.
But the visitors did not break stride, and with just over a quarter of an hour gone, a driving run from Messi saw him surge past multiple defenders on his way into the area, where he finished calmly into the bottom corner to equal Muller’s record.
Betis nearly conceded again within moments of the restart, but were thankful to goalkeeper Adrian for holding his nerve to tip a clever lob from Andres Iniesta over the crossbar.
Their resistance would not last long though, and when a one-two saw Iniesta tee up Messi inside the area with a delightful back-heel, the Argentine’s finish for his 86th goal in 2012, and his place in the footballing pantheon, was inevitable.
Adrian was called into action again to deny Xavi from 20 yards out, but just when it seemed like Barca were set to run away with the game, Betis managed to pull a goal back shortly before half-time.
The Blaugrana’s defence was nowhere near as organised as their attack, as Jordi Alba failed to read the offside trap set by the rest of the back-line, allowing Castro in behind to slot comfortably past Valdes.
Pepe Mel’s team started the second period strongly, and behind a raucous home support controlled possession and created chances as they pressed the Barca goal.
Valdes nearly gifted Betis an equaliser shortly after the interval after spilling a harmless cross from Sevilla, before recovering just in time to claw the ball around the post ahead of the onrushing Castro.
And with 20 minutes remaining, a wayward defensive header from Javier Mascherano from a Betis corner saw the ball rebound off the inside of the post and into the grateful arms of Valdes.
Matters were whipped into a frenzy with a flurry of chances during the closing stages. First, Pedro was slipped into space by Sanchez, but he could not direct his finish home as Adrian was able to block.
Pozuelo then crashed a 20-yard half-volley off the woodwork, a let-off which was soon matched by Barca as Messi blasted a shot on the turn onto the post, before Alba directed the rebound onto the crossbar from point-blank range.
Thiago thenblasted a shot into orbit from eight yards out as the scoreline somehow remained intact. The final whistle signalled three points to the Catalans and ensured they restored their six-point lead over Atletico Madrid, while Betis sit in fifth spot.