La Liga: Barcelona 5 Levante 0
The Argentine talisman supplied the first goal for Neymar before going on to claim a 23rd top-flight treble, as Luis Enrique's side made it 11 consecutive wins in all competitions.
A cool side-footed finish past Diego Marino doubled Barca's lead before Messi then applied a close-range finish from Pedro's assist to make it 3-0.
When Ivan Lopez brought down Neymar in the box after 65 minutes, Messi sealed his hat-trick and then substitute Luis Suarez rounded off the scoring with a well-executed scissor kick.
It marked a wholeheartedly positive afternoon's work for Luis Enrique and, in particular, his star forward.
Despite making eight changes from Wednesday's Copa del Rey win over Villarreal, Barca and Messi began on the front foot. The Argentina international and Ivan Rakitic both went close with efforts from outside the area early on.
Levante initially managed to frustrate their hosts, but Neymar broke the deadlock after 17 minutes when he converted Messi's lofted cross from the right for his 24th goal of the season.
From there, it was almost all one-way traffic.
David Barral did go close to levelling five minutes before the half-hour mark, but the midfielder dragged his shot wide before Messi got on the scoresheet and took centre stage.
Following Marc Bartra's pass, the three-time FIFA Ballon d'Or winner found the target to cap his landmark in style, as he slipped the ball under the onrushing Marino.
Messi could have made it three had he not scooped a strike over from inside the area late in the first half, but he threatened again early in the second period.
Neymar's cut-back was just too short for the waiting forward, but it seemed only a matter of time before he struck again.
That star pair continued to pose Levante problems, and Marino was required to intervene and end a slick piece of interplay before the hour mark.
Pedro - also marking a career landmark with his 300th Barcelona appearance - supplied the assist for Messi's second.
His hooked pull-back gave the little playmaker the simplest of finishes, before Messi sealed one of his more routine hat-tricks after 65 minutes.
A foul from Lopez on Neymar gave Messi the chance to score from the penalty spot, taking his Liga record to an incredible 269 goals from 300 games.
Not content to simply leave it at that, Luis Enrique opted to make changes, as Suarez replaced Neymar with time running out.
The Uruguayan's introduction soon yielded a fifth goal too when, with 17 minutes left, he acrobatically fired home from inside the area as Barca moved back to within a point of leaders Real Madrid, while Levante stay in the bottom three.