Lyon were Wednesday night's sacrificial victims.
The Argentinean started the blooding in the 17th minute with a ritual humiliation. For his penalty, he opted for a nonchalant lob down the centre. Lyon goalkeeper Anthony Lopez, having plunged to his left and stricken on the turf, could only look over his shoulder as the ball span almost sneeringly into the unguarded goal.
Lyon appeared to be on the verge of repaying such insolence after Lucas Tousart made it 2-1 after 58 minutes.
For a good quarter of an hour, Barcelona appeared nervous and the visitors spurned several chances to level at 2-2 and regain the initiative courtesy of their two away goals.
Twelve minutes from time, Messi imposed his pomp on the circumstances. Picking up the ball he surged into the penalty area, bamboozled the defenders Marcelo and Jason Denayer and fired at goal.
Substitue goalkeepr Mathieu Gorgelin got a hand to the shot but the ball trickled over the line.
His assists for Gerard Piqué's and Ousmane Dembélé's goals were equally mesmerising.
"There's no dishonour in losing at Barcelona," said Lyon defender Fernando Marçal after the match.
"But conceding five makes it look far worse than it was. We have to now concentrate on Ligue 1 and finish in the positions that get us into next season's Champions League."
Bruno Genesio's side lie in the third and final place for next season's competition with 10 games remaining.
Barcelona are likely to be in the 2019/2020 competition as Spanish champions. They lead La Liga by seven points with 11 games left.
The Catalans go into Friday's draw for the last eight as the sole Spanish representative, along with Juventus, Manchester United, Manchester City, Liverpool, Tottenham Hotspur, Porto and Ajax.
"Lionel played an incredible match, extraordinary," said Barcelona coach Ernesto Valverde. "He made assists, scored goals, won the ball back. "We are used to him, but somehow he always surprises us."
If the football gods are in wry mood, Barcelona and Juventus will be pitted together in the last eight.
"Not just in results, but having Leo on your team makes you feel like you can face anything," said Piqué.
Even Cristiano Ronaldo?