Barca were dominant from the start, as Anthony Lopes leaped across goal to plug out Lionel Messi’s curling effort on five minutes.
In stunning fashion, Barcelona surged forward with a Panenka penalty from Messi following a foul on Luis Suarez in the 17th minute.
Barca’s advantage in the overall tie increased on 32 minutes when a square ball from Suarez found Phillipe Coutinho, who needed no second invitation for an easy tap-in.
A worrying head injury to goalkeeper Anthony Lopes forced the visitors into a substitution just before halftime, with Mathieu Gorgelin taking over between the sticks.
The hosts pressed forward for more goals, but Gorgelin quickly stamped his ground to deny Messi’s low shot on 42 minutes.
The heavens looked to open for the French side just before the hour mark when Lucas Tousart finished into the bottom corner from poor defending by the Catalans to reduce the deficit.
Twenty minutes from time, Messi and Coutinho combined to restore the two-goal advantage, but after rounding Gorgelin, the Brazilian blasted into the side-netting.
The two-goal lead was eventually restored with 11 minutes remaining, as Messi danced through the Lyon defence to squeeze home a right-footed effort.
Spaniard Gerard Pique turned home Messi’s cross on 81 minutes to make it 4-1 on the night as the home side began to run riot.
The fifth goal arrived five minutes later, with Ousmane Dembele sending a low strike through Gorgelin’s legs to round off a comfortable night at the Camp Nou.