Unbeaten in eight home games in this competition, Lyon’s record looked under threat in the opening minute when Javi Rueda was caught inside the area by Nicolas Tagliafico, only for referee Irfan Peljto to wave play on.
The opening 15 minutes failed to see either side register a shot, but only thanks to Roman Yaremchuk’s shoe size being a couple of sizes too small to turn home an Endrick cross.
And following their earlier reprieve, Lyon weren’t so lucky when Rueda was caught again in the 19th minute, as this time Peljto showed Moussa Niakhate a straight red card.
Celta attempted to make their man advantage pay dividends soon after, as Pablo Duran latched onto a through ball and tried his luck from a narrow angle, before Williot Swedberg unleashed a low effort from 10 yards, yet both were thwarted by Dominik Greif.
In the final 10 minutes of the half, Fer Lopez did excellently to take the ball down and find shooting space, but again, there was no getting past Greif.
That ensured Les Gones got to the interval on level terms, and with the half-time result replicated at 90 minutes in seven of their last eight UEL home games, the signs were pointing to this game going the distance.
That only looked more likely after the first 15 minutes of the second half, as Endrick sent a 25-yard free-kick over the top, and Sergio Carreira saw his stabbed shot shuffled behind by Greif, only for the 11 men to go ahead just after the hour mark.
Carreira did well to hold off a challenge and square the ball across the six-yard box, where a deflection took it away from Iago Aspas, but Rueda was following up to bundle the ball home.
The tie could have been all but settled three minutes later as a Carreira effort went narrowly wide, and probably should have been when Rueda was through on goal, only to get caught in two minds and fail to square to a teammate instead of taking a shot.
Paulo Fonseca’s side threw bodies forward in the final 10 minutes, but a tame Corentin Tolisso header was all Ionut Radu had to deal with, as Os Celestes wrapped things up in added time when Ferran Jutgla coolly slotted home.
As a result, Claudio Giraldez’s side have suffered just one defeat in their last 10 away matches. They are now one round shy of equaling their best result in the UEL, while Lyon - for whom Tagliafico was dismissed in the final seconds - have gone seven games without a win in all competitions.