The Argentine curled home a trademark free-kick to reach the mark in just his 289th La Liga appearance and give Barcelona the lead against Sevilla.
Legendary Basque striker Zarra scored his 251 goals for Athletic Bilbao during a 15-year career from 1940 to 1955.
Messi's strike ended an uncharacteristically long three-game goal drought in league action as Barca slipped to defeats against Real Madrid and Celta Vigo and had to come from behind to beat Almeria 2-1 before the recent international break.
However, in between times, he had also equalled Real Madrid legend Raul's all-time record mark of 71 Champions League goals with a double against Ajax earlier this month.
Barca boss Luis Enrique hailed the 27-year-old as "the best player I have seen in my life" after he hit that landmark in Amsterdam.
Messi recently celebrated the 10th anniversary of his debut with the Catalan giants, a period which has seen him win 21 trophies and crowned World Player of the Year four times.
However, he cast some doubt on his future with the club this week when he refused to rule out a move away from the Catalan capital before the end of his career.
"Football is full of unexpected twists and turns," he told Argentinean newspaper Ole.
"It is true that I said I would like to stay there forever, but sometimes not everything turns out the way you want."
Messi's Real Madrid rival Cristiano Ronaldo, who is just one shy of he and Raul in Champions League goals, lies ninth on the all time La Liga list with two goals in Real's 4-0 win over Eibar on Saturday took him to 197 goals in just 177 games.