Didier Drogba had given the Premier League club the advantage with a neat finish early in the second half, but Eren Derdiyok equalised soon after, and Manuel Friedrich gave the Bundesliga outfit all three points in injury time.
The result moves Leverkusen into top spot of Champions League Group E, whilst The Blues drop to second and are level on points with Valencia.
Unai Emery’s team destroyed Genk 7-0 in the other pool game, with Spain international Roberto Soldado grabbing a hat-trick.
With Chelsea to host Valencia at Stamford Bridge in the last game of the group, it is a do-or-die clash for the English team, but Villas Boas feels confident his team can still progress.
“We believe in what we do, we believe in the talent of these players, we believe in them and that talent that is going to take us through to qualification – of course,” he told Sky Sports.
“Any negative result is difficult, we were organised and compact, but we have conceded on the details and that has made the difference, we have to improve our focus and concentration levels.
“We thought we had the game in our hands at 1-0 as we were compact and solid and had good chance for 2-0 but we didn’t take the chance and eventually paid heavily in the last minute.
“Obviously with the run of defeats you improve your work, focus and determination because at the moment it is not sufficient.
“I think we defended well as a team in the 90-minutes – the first goal we lacked concentration and on the set-plays when you are not tuned to it, and even if you are, players can anticipate you and they made the most of the opportunity they got to take an unfair result in my opinion but that is the reality, a defeat where we should have got something – it is not happening for us,” he concluded.
Chelsea have Wolves at home on Saturday, and simply must pick up three points to stop the bad run of form.
By Gareth McKnight