Modest Numancia are the only team to have beaten Barca in the league, winning 1-0 at home on the opening day of the season, and they made life difficult for their hosts early on.
After the break, however, Messi, twice, Samuel Eto'o and Thierry Henry all scored as Pep Guardiola's side stepped up a gear, and they moved to 53 points from 20 games.
Jose Barkero's blistering freekick for the visitors had made it 2-1 after 61 minutes.
"I congratulate Numancia. Their team knew what they were doing on the pitch, but Barca are lucky to have good players who can make a difference in a game, and they delivered the victory," Guardiola said.
The visitors were rewarded for their ambition when substitute Dady scored from close range following an error by Pascal Cygan in the 65th minute, cancelling out Giuseppe Rossi's stylish first-half opener.
Iniesta threaded through for Eto'o to notch his 19th goal of the campaign soon after, before Barkero pulled one back, but it was only a brief respite from Barca's constant pressure.
Henry bagged the third from Messi's run and pass, and the Argentine made it 4-1 as he squirmed through two defenders and rounded the keeper to score. Messi was denied his hat-trick near the end when he hit the crossbar.
