The Catalan giants prevailed following the goalless first-leg draw in France in their round-of-16 tie.
Barcelona’s talismanic Argentinian set them on their way yesterday.
Messi bagged a brace, including a cheeky panenka penalty, and two assists as he bossed the game in typical fashion.
The five-time Ballon d’Or winner responded to Cristiano Ronaldo’s hat-trick for Juventus on Tuesday with his own devastating display.
And the 31-year-old’s quality ultimately proved too much for Lyon as they crashed out of Europe.
The Ligue 1 side did cause Barcelona some genuine scares, though, as they fought to stay in the Champions League.
After Messi’s opener from the spot and Philippe Coutinho’s simple finish for the hosts’ second, Lyon stunned the Nou Camp with a goal of their own to blow the tie wide open.
Barcelona’s win last night came as:
“There was a bit of suffering after they made it 2-1”
Just before the hour mark, Lucas Tousart struck the ball past goalkeeper Marc Andre ter Stegen after Barcelona failed to clear the ball from a corner.
Another for Lyon would have seen them through on away goals, but Messi was the man to calm the fans’ nerves by regaining Barcelona’s two-goal advantage 12 minutes from time.
He jinked into space on the edge of the box before striking low and squeezing the ball under the grasp of substitute goalkeeper Mathieu Gorgelin, who had replaced Anthony Lopes in the first half.
After the game, Messi analysed the match and told Spanish newspaper Marca: ”We went for the match from the start and moved the ball around well.
“There was a bit of suffering after they made it 2-1, as we’d made it tough for ourselves at a set piece.
“They hadn’t done anything until then.
“Luckily we then made it 3-1 and we could be calm again.
“The goal for the 3-1 had a bit of suspense, but luckily the ball made it.
”At 3-1 we found a lot more space and we could come out quickly on the counter attack.”
Barcelona and Messi will discover their quarter-final and potential semi-final opponents tomorrow when the draw takes place in Nyon, Switzerland at 11am UK time.