With 90 minutes played, it looked as if Chelsea were to draw away 1-1 for the third time in this group stage but then the home team struck a sickening blow, scoring from a corner to leave just a point covering the top three sides going into the final games.
After a largely forgettable first half in which Michael Ballack had hit woodwork for the Germans, again from a corner, it was Didier Drogba who fired the Blues ahead early in the second half.
Cech then kept Ballack out with two fine saves but it still proved a lead Andre Villas-Boas's side could not hold onto, Leverkusen equalising with 72 minutes played of what had been a fairly even encounter. Chelsea had chances to restore the lead but it was Leverkusen who took theirs.
A win or a 0-0 draw at home to Valencia in two weeks' time is now imperative.
Ashley Cole suffered an ankle injury in training so did not take part. He is rated as a 60 per cent chance of making the game against Wolves at the weekend. Ryan Bertrand is ineligible for the Champions League squad so Jose Bosingwa was asked to play left-back with Branislav Ivanovic on the right.
Bayer Leverkusen made four changes from the side that lost at Stamford Bridge, three in defence where only Michal Kadlec remained. Gonzalo Castro came in on the right of midfield. Michael Ballack started complete with Cech-style nose mask.
Leverkusen had the early territorial advantage but with little menace to their attack. Chelsea's first foray forward floundered on a lack of understanding between Lampard and Bosingwa down the left.
On 12 minutes Sturridge escaped into space in the box and hammered the ball square but Leno in the home goal caught well.
There was an interruption just past the quarter-of-an-hour mark when David Luiz went down hurt having challenged for an aerial ball that had come back off Bosingwa. The stretcher came on but wasn't need as the Brazilian walked off the pitch for treatment. He continued soon after.
The cagey start to the game continued past the halfway mark in the first period. Chelsea won a free-kick over 30 yards from goal but Lampard's ambitious attempt had far too much height on it.
Chelsea's first shot on target came in the 29th minute - a Drogba free-kick but it was comfortable for the keeper.
Three minutes later Chelsea were far more concerned when Ballack got to a corner first and from close range, headed against the bar. The former Chelsea midfielder's aerial prowess is not diminished.
The home side's centre-forward Kiessling had been losing out to Terry in the physical contest so far and when he dropped deeper, his foul on Bosingwa earned him a booking.
It had been an even contest for a while but as half-time approached there was the promising sign of Chelsea finishing the half the stronger side.
Drogba had the best Chelsea chance so far when he was put through on the right side of the area by a touch of Sturridge class but from out wide the Ivorian shot over. It wasn't a straightforward chance but was one well within his capabilities.
Then with three minutes remaining Sturridge held the ball in an advanced position, allowing Mata the chance to shot but without the power to beat the keeper. That was another presentable chance. Chelsea moved forward quickly once more and after Lampard had been halted in front of goal, Sturridge tried to curl one in from distance but Leno claimed.
Late on Ballack was shown a yellow card for dissent, Kadlec having earlier gone in the book to make it 3-0 on cautions at the interval.
Drogba may not have made the most of it the first time Sturridge had set him up with an opening but he was making no mistake second time. In possession with his back to goal 15 yards out, he was initially well policed but then turned inside in trademark style and found the bottom corner.
Ivanovic then tried to hammer home the advantage but his shot from distance was too straight, The Serbian then became Chelsea's first booked player for a foul on Sam.
For a minute just before the hour, the game turned into a duel between the two masked men, first Cech tipping over at full stretch after an adept bicycle kick by Ballack, and then when the same player got on the end of a ball into the six-yard box, it looked for all the world a goal but Cech somehow parried from point-blank range.
There was an escape soon after as substitute Schurrle headed straight into the Chelsea keeper's arms.
It was a strong few minutes by Bayer but when Terry cleared a Ballack cross, Sturridge was able to use his pace to run from his own half past his marker. He made space outside the last defender but couldn't then beat the keeper.
Malouda and Alex were introduced in quick succession, Mata and David Luiz making way. Bayer made a change too, Derdiyok coming on and it paid off almost immediately for the home team.
Sam was the player who was found in space on the left and with Cech exposed and covering the potential shot, the winger chipped the ball over to Derdiyok at the far post who headed in. There were 72 minutes played.
Drogba thought he should have had a penalty when he was tumbled in the box as Chelsea looked for a response but there was nothing given. The game was very much in the balance.
It looked to be opening up for Chelsea when Malouda floated a ball over to Drogba who was not tightly marked but he volleyed wide. Instead it was the home side who snatched it as stoppage time began. From a corner, Friedrich got above Alex on the penalty spot to head in off the underside of the bar.
Chelsea (4-2-3-1): Cech; Ivanovic, D Luiz (Alex 68), Terry (c), Bosingwa; Ramires, Meireles (Mikel 79); Sturridge, Lampard, Mata (Malouda 65); Drogba.
Unused subs Turnbull, McEachran, Kalou, Torres.
Scorer Drogba 47.
Booked Ivanovic 54, Meireles 71.
Leverkusen (4-2-3-1): Leno; Schwaab (Schürrle 56), Friedrich, Toprak, Kadlec (Derdiyok 70); Bender, Rolfes (c); Castro, Ballack, Sam; Kiessling (Oczipka 81).
Scorer Derdiyok 72, Friedrich 90.
Unused subs Giefer, Reinartz, Ortega, Jørgensen.
Booked Kiessling 35, Kadlec 39, Ballack 43.
Referee Viktor Kassai from Hungary.