Having come away from France with a memorable win, Chelsea were in a strong position going into the second leg, but knew they needed a gladiatorial performance.
Lyon, who have dominated European football for the last decade, came with serious intention and should have scored within a matter of minutes.
Delphine Cascarino forced a save from Berger, before Chelsea captain Magdalena Eriksson’s poor clearance set up Signe Bruun, but the Lyon striker sliced it over the bar.
The hosts eventually settled and Sam Kerr had a glorious opportunity when she was slid in one-on-one with Endler, but the goalkeeper came out on top.
It felt inevitable more chances would follow and they both fell Lyon’s way – Gilles then Dabritz silencing a nervy Stamford Bridge crowd.
The holders, who were able to bring on star striker Ada Hegerberg at half-time, still looked vulnerable, however, and as James dribbled into the box in injury time at the end, supporters were on their feet in anticipation.
Chelsea will now need to produce another giant-killing in the next round as Barcelona, who beat them in the 2021 final, await. Arsenal take on two-time champions Wolfsburg, with the prospect of an all-English final.