AC Milan hold a commanding 2-0 lead after the first leg of their last-16 tie but Saturday's match at the Nou Camp saw normal service resumed as a strong second-half display ended with Barcelona 15 points ahead of Atletico Madrid who play Sunday.
However, it was Sevilla who took the lead through Alberto Botia in the 42nd minute before two goals in eight minutes turned the game on its head.
David Villa equalised when he nodded home in the 52nd minute on his return from a kidney stone operation before Messi scored his 38th league goal of the season eight minutes later.
Andres Iniesta got a sight of goal in the fourth minute when he received the ball in the penalty area and cut inside but his attempt was blocked by Federico Fazio.
Dani Alves then found himself in space on the right outside the area and his shot was on target but it took a deflection and looped over the goalkeeper - but on to the roof of the net.
It took Messi until the 22nd minute to have his first real shot on goal, the Argentinian losing his marker on the right of the area and collecting a dinked ball with his left foot before shooting with his right and forcing Antonio Beto to go down quickly to block.
However, it was Sevilla who took the lead in the 42nd minute.
Andujar Coke controlled the ball on the right of the area and his high cross found Botia who rose above two defenders and headed the ball powerfully down and into the net.
The goal galvanised Barca and Iniesta wriggled past his defender before slotting a ball in front of goal which evaded everybody and the game reached half-time with the visitors ahead.
The home side were noticeably slicker after the break and from the outset had their visitors pinned back.
So it was not a surprise when they equalised seven minutes into the second half.
Alves collected the ball on the right and, looking up, produced a pinpoint cross which found Villa in front of goal after he had stolen between two defenders and all he had to do was nod home.
Eight minutes later Barcelona were ahead and unsurprisingly Messi was the scorer.
Despite Sevilla packing the area, Cristian Tello fashioned himself space on the left and he slid the ball back for the Argentinian, who had lost his markers, and he slotted home a low shot.
Manu reminded Barca they were still a threat when he sent in a fierce shot which forced Victor Valdes into a flying save to his left.
It should have been 2-2 with a little more than a quarter of an hour left when Alvaro Negredo collected a through ball from Ivan Rakitic and raced ahead of his defenders.
But with Valdes rushing out at his feet, Negredo clipped the ball not only over the keeper but also over the bar with the goal gaping.
Sevilla were then two on two with the defenders but Rakitic got the ball tangled up under his feet and Barca calmly cleared.