Leverkusen are in ninth place in the Bundesliga after an erratic campaign and risk losing out on European action altogether next season.
They travel to Atletico Madrid on March 15 for the return leg of their Champions League round-of-16 match after a 4-2 loss at home in the first leg last month.
"Due to the current sporting development we reached the conclusion after a long analysis that parting ways may be painful but unavoidable for the further development of Leverkusen," said the club's managing director Michael Schade.
News that makes sense
Your trusted source for staying up-to-date with the world around you. Get free daily news updates and analysis, straight to your inbox.
(Reporting by Karolos Grohmann; Editing by Clare Fallon)
