The Argentine international who recovered from a knee injury to start the game, scored his first goal in the 16th minute with a sweet left footed shot into the bottom right corner of the goal from the centre of the box, following an assisted by Andres Iniesta.
That goal saw him pulling equal with the great Muller.
Nine-minutes later, Messi made it 2-0 and took the record when he finished off a clever looking heel pass from Iniesta – firing past Adrian for his 86th goal this year.
Barcelona, meanwhile, have lost Cesc Fabregas, who came off the pitch injured and was replaced by Alexis Sanchez, who only just returned from an injury setback him.
Ruben Castro has scored for Real Betis.