Andre Villas-Boas' side set up a last-16 tie against Inter with an equaliser right at the death after Maxime Gonalons had looked to have decided it with an early headed goal
Maxime Gonalons gave the Ligue 1 side the lead after 17 minutes when he headed in Clement Gernier's free kick and it seemed that Samuel Umtiti's away goal from the first leg would be enough to see Lyon through on aggregate. That was until Mousa Dembele's thunderbolt right at the death dramatically turned the tie on its head and set up a meeting with Inter.
Andre Villas-Boas made one change to the Spurs side who won the first leg 2-1, Clint Dempsey dropping to the bench with Lewis Holtby called in. Lyon boss Remi Garde also made one alteration, opting Gernier ahead of former Spurs midfielder Steed Malbranque.
But Gernier's next ball did result in a goal. The 22-year-old's free kick from the left-hand side was fired in towards the front post where club captain Gonalons was on hand to head past Friedel and level the aggregate score.
Lyon's away goal in the first leg meant that Spurs had to score as a result but Villas-Boas's men were struggling to test Remy Vercoutre.
Instead it was Lyon who threatened to score a second and perhaps could have done had Fofana taken more care with his through ball for Bafetimbi Gomis. Lisandro Lopez also wasted a chance when he failed to find the target after meeting Lacazette's cross in the area.
Spurs did come close just before the break though, Holtby had a low shot hit from just outside the area tipped on to the post by Vercoutre.
The visitors came out on the front foot in the second half and had a glorious chance to go level when Adebayor found Bale unmarked after a swift counterattack but the Welshman hit his first-time finish inches wide of the post.
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Referee Wolfgang Stark then made two big calls as he waved away penalty appeals from both sides, before Bale and Adebayor both came close to scoring for Spurs.
The Togolese hit the top of the bar with a cross moments before the Welshman stung the hands of the Lyon keeper with a drive from range.
Clint Dempsey, a late substitute, had two decent chances in quick succession in the final 10 minutes but failed to find the target with either effort.
Lyon looked to be strolling into the next round when, out of nowhere, Dembele shocked the Stade de Gerland with a powerful long-range strike on the stroke of full-time.