The Argentine World Player of the Year netted his 85th and 86th goals of 2012 in an entertaining game at the Benito Villamarin in Seville to overhaul the previous best of 85 set by German Gerd Muller in 1972.
Messi's exploits overshadowed those of Atletico striker Radamel Falcao, who earlier put bottom side Deportivo La Coruna to the sword with a five-goal haul in a crushing 6-0 home success.
The prolific Colombian, known as 'the tiger' and coveted by many of Europe's richest clubs, took his tally for the season to 16 in 15 matches as Atletico restored a five-point advantage over city rivals Real Madrid.
Jose Mourinho's Real side had to twice come from behind to scrape a 3-2 win at Real Valladolid on Saturday which closed the gap to Atletico, who they beat 2-0 at the Bernabeu last weekend, to two points overnight.
However, Atletico responded by romping to a 12th win in 15 outings this term against a promoted Depor side in danger of dropping straight back to the second division.
Barca have won all their games this season apart from a 2-2 draw at home to Real in October and Messi's double put them on 43 points, with Atletico on 37 and Real on 32. Betis are fifth on 25 points, level with fourth-placed Malaga, who thumped Granada 4-0 on Saturday.
"It seems impossible that he [Messi] can score that quantity of goals in a year but there are three matches left and we hope he keeps increasing his tally," Barca coach Tito Vilanova told a news conference.
"We hope he has a long way to go in his career because he is very young," he added. "I don't think we will see another player like him."
UNFORTUNATE ANDALUSIANS
Vilanova's side predictably dominated Betis for most of the first half but lost control after the break and the unfortunate Andalusians were three times denied by the frame of the goal.
Messi equalled Muller's record when he picked up the ball in a central position in the 16th minute and left the Betis defence standing before sending an angled shot across goal into the bottom right corner.
Andres Iniesta's clever backheel set Messi up to score again nine minutes later with a sweeping strike from a similar position just inside the penalty area that flew into the same corner of the goal.
Ruben Castro pulled a goal back for the home side in the 39th minute to set the stage for a difficult second half for the visitors.
Messi came close to a hat-trick around five minutes from time when he spun in the area and Betis goalkeeper Adrian turned his shot onto a post before Jordi Alba struck the rebound off the top off the crossbar.
The defeat was tough on Betis, who beat Real 1-0 at home last month and gave Barca one of their toughest workouts so far this season which deserved at least a point.
Atletico forward Diego Costa made amends for Thursday's Europa League red card when he opened the scoring at the Calderon with a header from Koke's corner in the 23rd minute.
Depor midfielder Juan Valeron hea
