For the third time on their travels in Group E, the Blues took the lead, Didier Drogba scoring only his second goal of the season shortly after half-time.
But, as against Valencia and Genk, the visitors threw away victory, substitute Eren Derdiyok equalising before Manuel Friedrich completed the comeback in stoppage-time.
To make matters worse, Valencia beat Genk 7-0 to wipe out Chelsea’s superior goal difference and leave Andre Villas-Boas’ men needing to win or keep a cleansheet in next month’s final group game to reach the last 16.
Chelsea arrived at the BayArena beset by on- and off-field problems and there was more bad news for the visitors when it emerged Ashley Cole, who had started all of their Premier League and European games this season, had been struck down by an ankle injury.
Jose Bosingwa was recalled as an emergency left-back, while Raul Meireles and Daniel Sturridge came into the side beaten by Liverpool on Sunday – but there was still no place for Fernando Torres.
David Luiz was retained at centre-half despite Gary Neville comparing his defending to a 10-year-old PlayStation gamer.
A boisterous home crowd almost had something to celebrate in the 32nd minute.
Former Blues favourite Michael Ballack rose highest to head Gonzalo Castro’s corner back acorss goal and against the crossbar, with Ramires on hand to clear.
Groans became whistles minutes later when Stefan Kiessling was booked for dissent and Drogba should have silenced the home fans completely six minutes before the break.
Daniel Sturridge, who rose above the general mediocrity, played an inch-perfect through-ball and Drogba rounded Bernd Leno before lashing wildly into the side-netting from a tight angle.
Michal Kadlec was cautioned for handball and Juan Mata sent a weak volley straight at Leno after more outstanding work from Sturridge.
Leverkusen were losing their discipline and Ballack became the third home player needlessly booked before half-time.
Chelsea picked up where they had left off and were in front inside three minutes of the restart.
Sturridge floated another fabulous ball in to Drogba, who brilliantly held off Friedrich before turning and rifling left-footed into the bottom corner for only his second goal of the season.
And the striker almost twice laid on a second when his flick-on was headed straight at Leno by Frank Lampard and his pass set up Branislav Ivanovic for a blast also too close to the goalkeeper.
Ivanovic was then carded for a late tackle on Sidney Sam before Leverkusen sent on Andre Schurrle for Daniel Schwaab.
Chelsea had thrown away a lead in both their previous Champions League away games and they went close to doing so again twice in a minute, only for Petr Cech to win the battle of the masked men.
The goalkeeper first tipped Ballack’s overhead kick over the bar before producing a brilliant reaction save to repel his former team-mate’s close-range volley.
Kiessling should have given Cech no chance with a point-blank header soon after which he somehow sent straight at the Czech as all Chelsea’s defensive uncertainty began to resurface.
Sturridge almost settled the nerves with a superb 60-yard run and finish that was close down by Leno before Mata was withdrawn for Florent Malouda and Luiz soon followed for Alex.
Malouda almost killed the game when he drove into the box but was thwarted by a sprawling save.
That came seconds after Leverkusen made their second change when Derdiyok replaced Kadlec – and it was the striker who levelled 17 minutes from time.
The ball found its way to Sam on the left and his cross drifted over Cech and the entire Chelsea defence, allowing Derdiyok to nod into an empty net.
Drogba was convinced he should have had a penalty when Lars Bender clattered into the back of him and he also sent a volley wide.
But with the final whistle looming, Leverkusen snatched victory, Friedrich leaping superbly to power Castro’s corner in off the crossbar.