Substitute Nabil Fekir and top scorer Alexandre Lacazette netted second-half strikes to earn Lyon an enthralling 4-2 win over Roma in the first leg of their round-of-16 tie in France.
Fekir struck less than four minutes after coming off the bench, dancing past two opponents before beating goalkeeper Alisson, while Lacazette grabbed a fourth with a stunning long-range strike deep into stoppage time.
Lyon went a goal up early on when Mouctar Diakhaby found the net after Mathieu Valbuena's free-kick from the right, but his error contributed to Mohamed Salah and Federico Fazio turning things around before half-time.
Corentin Tolisso then struck early in the second half to begin the hosts' revival, before Fekir and Lacazette sealed the win late on in a hugely entertaining encounter.
The Ligue 1 giants will have fancied their chances heading into Thursday's encounter following their excellent form at the Parc Olympique Lyonnais in recent weeks, with Bruno Genesio's men netting an impressive 24 goals in their last five home games.
Roma, meanwhile, were relatively low on confidence after winning just one out of their last four matches in all competitions, losing the other three.
However, Luciano Spalletti's men got an early chance to open the scoring through Radja Nainggolan, but Anthony Lopes did well to deny the Belgium international and Lyon moved ahead in the eighth minute. Rafael flicked Valbuena's set-piece to the back post and Diakhaby was on hand to guide the ball past Alisson.
The away side immediately started pushing for an equaliser and Salah levelled in the 20th minute after a mistake from Diakhaby, the Egypt international making the most of the Lyon defender's slip as he aimed a low shot through Lopes' legs.
Spalletti's side continued to cause the Lyon defence problems and Fazio put Roma ahead shortly after the half-hour mark with a powerful header following a fine cross from veteran midfielder Daniele De Rossi.
Lyon refused to throw in the towel, though, and Tolisso restored parity early in the second half, finding the net with a precise strike from just outside the box after a quick one-two with Lacazette.
Alisson came to the fore to keep out Maxime Gonalons' deflected long-range effort, before pulling off another smart stop to keep out a powerful strike from Lacazette.
But Lyon got their third goal after all when Fekir showed his class with 16 minutes left, the substitute shaking off two opponents inside the area before placing a low shot past the helpless Alisson.
Lyon kept on pushing for more in the dying minutes and they were rewarded for their positive approach when Lacazette blasted into the top corner in the 92nd minute to give his side a two-goal lead ahead of next week's return at the Stadio Olimpico.