Liverpool substitute Ryan Babel scored a stunning goal in the 83rd to make it 1-0, but Lopez found space in the penalty area and coolly clipped his shot over goalkeeper Pepe Reina to severely damage the Reds' chances of progressing.
Babel picked up the ball about 25m out and hit a swerving shot into the top corner past goalkeeper Hugo Lloris.
Lyon team leads Group E with 10 points, one more than Fiorentina. Liverpool has four points and must win its final two games to have any chance of progressing.
"You have to be really disappointed because it was a great opportunity, we had our chances," Liverpool manager Rafael Benitez said. "Again a late goal against Lyon, (it makes) a massive difference.
"It's difficult but not impossible (to qualify). We have to win our first game and see what happens between Fiorentina and Lyon. We've done it in the past."
Benitez wouldn't say whether one of Lyon's players was in an offside position in the build-up to the goal, preferring instead to argue that his team should have defended better.
"I haven't seen the replay but clearly we made a mistake. We had a lot of players around and we had to do better," Benitez said. "If we are winning and in control, we have to keep the ball sometimes."
Lyon coach Claude Puel jumped off the bench and pumped his fist in delight as Lopez's goal meant Lyon joined Bordeaux in the knockout stage after just four group games, capping a good week for French clubs with Marseille thrashing FC Zurich 6-1 on Tuesday.
"It was a very hard game for us, we started well but then we let this Liverpool team get back into it," Puel said. "We started a lot better in the second half, and paradoxically that's when they scored. But we showed great courage to come back. The players are really tired tonight but really happy they are through now."
Five-time European Cup winner Liverpool looked a shadow of the team that won the Champions League in 2005 and finished runner-up in 2007, clearly lacking inspiration without its injured captain Steven Gerrard in tandem with Fernando Torres.
Lyon winger Michel Bastos found space to fire a shot that was easily grabbed by Reina in the fourth minute, but Torres should have done better in the 12th when he swung at a cross from the left and placed a low shot straight at Lloris.
"When a player is playing with pain it is not easy," Benitez said. "He was very inconsistent because he had to stop and start again. Hopefully, he'll be OK. We'll be working hard with him."
Puel had to make two changes before the break, with right back Anthony Reveillere - who had been doubtful because of a calf strain - coming off after only 19 minutes and replaced by Lamine Gassama.
"We lost two players and of course it's tough, we went through everything tonight," Puel said. "We couldn't really develop our game because of these injuries."
Lloris, who made some outstanding saves in the 2-1 win at Anfield two weeks ago, made another good stop with his legs to block Andriy Voronin's shot after he ran clean through in the 28th.
Liverpool defender Daniel Agger, who shook off a back injury to play, received a yellow card after chopping down striker Bafetimbi Gomis on the half way line when midfielder Miralem Pjanic had chipped a ball over the top.
Pjanic then limped off shortly before half time after taking a knock, leaving Lyon short of creativity in midfield.
Reina was called into action when Gomis ran through, having to sprint outside his penalty area to head the ball away early in the second half. Lloris made a brilliant one-handed save to keep out a curling shot from Liverpool midfielder Lucas in the 67th.
"You can see the level he has. He is decisive for us," Puel said. "But you shouldn't single out one player, the whole team helped us tonight."
Benitez replaced the ineffective Voronin with Babel with 20 minutes left, and the tired Gomis made way for France winger Sidney Govou shortly after. Govou lost the captaincy recently after a late-night drinking spree at last week's Lyon tennis tournament.
Moments after Govou's introduction, Lopez found space inside the penalty area and forced Reina into a sharp save.
