Ousmane Dembele doubled Barca's lead with a curling finish before Luis Suarez made it 3-0 from a tight angle. A goal in each half with an assist in between saw the 5th best player in the world, according to France Football, break another La Liga record.
Barcelona coach Ernesto Valverde, whose side host Tottenham in their final Champions League group game on Tuesday night, had warned of a "trial by fire" in the build up to the derby fixture and things could have been different had Borja Iglesias not shot wide early on.
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Messi was leading Espanyol a merry dance and he set up Barca's second in the 26th minute, twisting and turning defenders on the edge of the box before slicing the back four open with a fine pass for Dembele, who cut inside and fired across Lopez into the top-right corner.
Lionel Messi celebrates against Espanyol (Joan Monfort/AP).
Messi had also set up Dembele's goal in the 26th, sending a well-placed throughball to the French forward.
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Goalkeeper Diego Lopez saved from Suarez, given the all-clear to play following a knee problem, as Barcelona looked to swiftly double their lead.
Victor Sanchez headed over the Barcelona crossbar 10 minutes from time as Espanyol continued to search for a goal, and it nearly arrived when Baptistao struck towards the far corner, but the ball just deflected wide.
Espanyol started the second period on the front foot, but aside from a Sergi Darder attempt which missed the crossbar, the home supporters did not have too much to shout about.
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Messi was in fine form against derby rivals Espanyol.