The contest was delicately poised following a goalless draw in the first leg, but Ernesto Valverde's side were far too strong for Lyon in the second leg, scoring through Lionel Messi (2), Philippe Coutinho, Gerard Pique and Ousmane Dembele.
Barca have not won the Champions League since 2015, but they will be present in Friday's draw and their performance on Wednesday night would have sent out a strong message to the rest of the competition.
The headline team news for Barca arrived in the shape of a Coutinho start, with the Brazilian chosen ahead of Ousmane Dembele, although it is understood that the decision was almost forced upon Valverde, with the latter not fit enough to start.
As for Lyon, Nabil Fekir missed the first leg through suspension, but the Lyon captain started in a team which also included Moussa Dembele and Memphis Depay, but Bertrand Traore was only on the bench.
Lopes then had to tip a Messi effort wide of the post two minutes later as the home side made a fast start to the second leg on home soil.
Lyon were coming under intense pressure, though, and again needed their goalkeeper in the 13th minute to palm the ball clear under pressure from Messi, who had been released into a dangerous position.
Barca did take the lead in the 17th minute, however, with Messi converting from the penalty spot after Luis Suarez had been clumsily brought to the ground by Jason Denayer.
Lyon could and probably should have levelled two minutes later when Depay found Moussa Dembele inside the Barca box, but Lenglet was across at the final moment to deflect the Frenchman's effort just wide of the post.
There was a fairly lengthy stoppage in the period that followed as Lyon goalkeeper Lopes received treatment following a head injury which he picked up in a challenge with Coutinho.
The 28-year-old briefly recovered, though, and pulled off another super save in the 29th minute to deny Luis Suarez, before Rakitic fired the rebound over the crossbar.
Barca were utterly dominant, however, and doubled their advantage in the 31st minute when the much-criticised Coutinho slotted a low Luis Suarez pass into the back of the net from close range.
Luis Suarez just missed the far corner with his own strike five minutes later as the pressure continued, with Lyon - who were ultimately forced to replace Lopes following his earlier challenge with Coutinho - unable to stem the flow of pressure that continued to head their way.
Mathieu Gorgelin was Lyon's substitute goalkeeper and the 28-year-old had to keep out a low Messi strike in the 39th minute, with 2-0 the score at the half-time interval.
Barca came incredibly close to scoring a third in the 47th minute when Messi lifted the ball over the onrushing Gorgelin, but Marcelo was on hand to clear the Argentine's effort off the line.
Lyon were having decent spells in possession as the match approached its hour mark, but Ter Stegen remained extremely comfortable between the sticks.
Fekir had a half-chance for the visitors in the 57th minute after finding space outside the Barca box, but the Frenchman's effort was always moving wide of the home side's post.
The Ligue 1 outfit were on the scoresheet one minute later, though, with Lucas Tousart finding the bottom corner with a super strike after Barca failed to clear a corner from the left. There was almost a three-minute delay as a possible offside was checked, but the goal was ultimately given.
Fekir missed the Barca crossbar in the period that followed as Lyon chased a second, which would, at that point, have sent the visitors into the quarter-finals of the Champions League.
Ferland Mendy then set up a shooting chance for Memphis, but the former Manchester United attacker lost his footing at the vital moment as Barca survived another dangerous moment.
Coutinho hit the side-netting 20 minutes from time, before being substituted moments later as Ousmane Dembele was introduced with his team in need of some assistance. Arturo Vidal quickly followed for the home side, while Traore was introduced for Lyon ahead of a huge final 15 minutes.
Messi ensured that Barca would have serious breathing room in the 78th minute, however, with the Argentine squeezing one through the gloves of Gorgelin. The hosts were not finished, though, and made it four three minutes later when Pique turned a low Messi cross into the bottom corner.
Four then became five in the 86th minute when Ousmane Dembele threaded a low effort through the legs of Gorgelin to send Barca into the last eight in impressive fashion.
BARCELONA (4-3-3): Ter Stegen; Roberto (Semedo 83'), Pique, Lenglet, Alba; Rakitic, Busquets, Arthur (Vidal 73'); Coutinho (Dembele 70'), L Suarez, Messi
LYON (5-3-2): Lopes (Gorgelin 35'); Dubois, Denayer, Marcelo, Marcal, Mendy (Cornet 78'); Ndombele, Tousart, Fekir; Dembele, Memphis (Traore 73')