Having won well on their own turf in last week's first leg they were strong favourites to progress, but last year's French champions Bordeaux made life difficult for them.
After Lyon's Michel Bastos fired two speculative free-kicks wide and striker Gomis headed over when he should have scored, the hosts began to stamp their authority on proceedings in front of a partisan home crowd.
Their first chance came courtesy of a viciously inswinging Wendel free-kick from the right that left Lyon keeper Lloris stranded, but Yoann Gourcuff could only glance over - the young midfielder showing his frustration by kicking the post.
Chamakh had been quiet but the striker suddenly burst into life with two shots inside the Lyon box that needed to be blocked, before Jaroslav Plasil blazed over from the edge of the 18-yard box.
Just before the break, Bordeaux captain Diarra turned up the volume even more inside the Chaban-Delmas stadium with a sizzling 30-yard volley that crashed against the bar, but they did not have to wait too much longer to go in front on the night.
Chamakh (left) bundles in Bordeaux's goal, but it was not enough
Benoit Tremoulinas surged down the left to receive a pass inside the area and after his cross was flicked on by Plasil, it was bundled home from inside the six-yard box by the predatory Chamakh.
The Bordeaux players left the field to rapturous applause, but the immediacy of the interval gave Lyon a chance to regroup and they began the second half in the ascendancy as Michel Bastos dragged off target from 20 yards.
It took Bordeaux a while to reassert their dominance once more, but they only needed one more goal to progress and as the half wore on they began to attack with greater regularity and urgency.
Wendel took the ball down 22 yards out and fired wide, before Chamakh thought he should have had a penalty after Cris appeared to bundle him over inside the Lyon area.
With the clock ticking down, Bordeaux had their best two chances - but a combination of poor finishing and superb goalkeeping cost them their chance of a last-four berth.
Firstly, a corner from the left reached the back post where an unmarked Sane could only nod wide from four yards, before Wendel's bullet-like header moments later forced a magnificent one-handed save from Lloris.
The keeper's heroics proved sufficient to secure Lyon's first-ever place in the last four, where they will face German giants Bayern.
Bordeaux coach Laurent Blanc: "It's more in the first leg that we have regrets - we did what we had to do in the second leg.
"I have regrets over the first leg where our lack of defensive experience cost us at least two goals."
Lyon coach Claude Puel: "It was a match that was not easy. Even though we told ourselves that we should play as it was 0-0 in the first leg, we felt a bit pressure.
"We were too much on the back foot in the first half. We handled better the second half because Bordeaux played at a slower tempo."
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