From there the floodgates opened, and although Messi should have been flagged offside, no call came as he controlled Ivan Rakitic's pass before cleverly turning David Lopez and rifling into the top corner.
Leo Messi was again the hero in the Camp Nou as he scored a hat-trick in the Barcelona derby, with Barca's remaining goals scored by Gerard Pique and a fit-again Luis Suarez, reports Xinhua news agency.
It only took 10 minutes for Messi to bag his second, thanks to an assist from Jordi Alba.
By the hour mark, the Argentine captain had made it 3-0.
While it took some time for Barcelona striker Luis Suarez to get on the scoresheet against Espanyol, the Uruguayan worldwide didn't seem much bothered about it, and instead felt privileged to play alongside Lionel Messi.
Earlier, Real paid for the absence of the suspended Cristiano Ronaldo and a series of missed chances by Gareth Bale as they were held to a shock 1-1 home draw by newly-promoted Levante.More news: Facebook: Russia-Linked Accounts Bought $100000 of Political Ads During 2016 Election
Villarreal had lost its first two games and was yet to score a goal, while Real Betis has now lost two of its first three matches.
Valverde had a two-year spell as an Espanyol player between 1986 and 1988, reaching the 1988 UEFA Cup final, and later guided Barcelona's city rivals to the 2007 UEFA Cup final, where they also lost on penalties, during a two-year tenure as coach.
Messi maintained his sizzling club form with goals in the 26th, 35th and 67th minute to propel the Blaugrana to the top of the league table with nine points from three matches. "It doesn't mean anything, but being ahead is always good".
With 20 minutes left of the game, Ernesto Valverde drafted on Barcelona's £97 million man.
"His team-mates know that he has real quality".