Both Messi and Real Madrid's Ronaldo have now scored 69 goals in the competition after the Argentinian followed up Neymar's first-half opener at the Nou Camp on Tuesday night.
He was later withdrawn with a view to keeping him fresh for Saturday's showdown at the Santiago Bernabeu and remains, along with Ronaldo, two goals shy of former Real striker Raul's record tally.
"Generally I liked the game," Barca coach Luis Enrique said.
"We were very much the better team in the first half. There were ten minutes when they could have got back into it, but they were ten very isolated minutes We ended up winning deservedly. We were much more powerful than our opponent."
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