The 56-year-old Dutchman had been in charge at the Bay Arena since the second half of the 2018/2019 season.
Leverkusen started the 2020/2021 season brightly but have tailed off since December and last weekend’s 3-0 defeat to Hertha Berlin in the Bundesliga saw them drop to sixth on the table.
They have also been knocked out of the Europa League by Young Boys of Switzerland and crashed out of the DFB-Pokal disappointingly to fourth tier Rot-Weiss Essen in early February.
"In view of the development of football in recent weeks, we have come to the conclusion that the separation from Peter Bosz can no longer be avoided," said sporting director Rudi Voller in a statement.
"The 3-0 defeat at Hertha on Sunday was unfortunately characteristic, our team has recently fallen into the same pattern over and over again.
"We haven't been able to put an end to the repetitive mistakes and get back on the road to success.
"After a factual and very open analysis of the sporting situation, we therefore agreed to make a change, despite the great appreciation for Peter Bosz."
The former Ajax Amsterdam and Borussia Dortmund manager will be replaced by former Stuttgart boss Hannes Wolf until the end of the season.
"I am very pleased with the trust that has been placed in me, because Bayer 04 is not just any club for me," Wolf said.
"Leverkusen has been one of the most attractive places in German football for many years. There is a highly ambitious environment here and a very talented, exciting team.
"We all have opportunities to get into the European positions. It's up to us to get the maximum out of the remaining eight games."