Having drawn three of their last five league outings, the leaders held a five-point advantage coming into Sunday's clash against second-placed Atletico at Camp Nou.
Diego Simeone's side had won eight and drawn one of their previous nine in LaLiga, but their momentum was halted by another milestone moment for the majestic Messi.
On 599 goals for club and country, the Argentine brought up the landmark in fitting style, bending a free-kick into the top corner midway through the first half despite a touch from goalkeeper Jan Oblak at full stretch.
It was the third successive league game in which Messi has netted a direct free-kick - the first time he has achieved that feat - and Barca could have had more at the end of a first half in which Atletico failed to muster a shot on target.
The only sour note for Barca was losing Andres Iniesta to an apparent hamstring strain in the opening period and, although Atletico improved after the break, Marc-Andre ter Stegen was barely tested, ensuring the day belonged to Messi and Barca.
For all Barca's dominance of possession in the opening 20 minutes, the only clear sight of goal came at the end of some trademark Messi magic.
The Argentine, seemingly penned in by Gabi, Thomas Partey and Filipe Luis, danced away from all three but could only fire a weak shot straight at Oblak from just outside the box.
Atletico's goalkeeper could do little about the opener five minutes later, however.
Thomas brought down Messi 25 yards from goal, to the right of centre, and the little maestro stepped up to curl the resulting set-piece over the wall and into the top-right corner.
Barca continued to turn the screw, Luis Suarez seeing an effort blocked by Jose Gimenez and the Uruguay forward was involved again soon afterwards, combining brilliantly with Philippe Coutinho only for the latter to fire straight at Oblak.
Iniesta was replaced by Andre Gomes before Coutinho stung the palms of Oblak again and, after the interval, Messi saw another free-kick blocked by the defensive wall.
Diego Costa and Antoine Griezmann had been largely peripheral figures for the first 73 minutes and when the pair finally did combine, the France international blazed high and wide from outside the box.
Oblak parried away Sergio Busquets' first-time volley from a corner soon afterwards and with five minutes remaining Atleti were rightfully denied an equaliser by the offside flag, with Costa straying beyond the last defender in nodding down for substitute Kevin Gameiro to smash home.
That frustration summed up Atletico's day as their hopes of a second LaLiga title under Simeone suffered a significant blow, with 11 matches of the league season now remaining.