Leipzig fired coach Domenico Tedesco on Wednesday, hours after a 4-1 home loss to Shakhtar Donetsk in the Champions League.
Tedesco led Leipzig to a first major title in its 13-year history - the German Cup last season - but a poor start to the Bundesliga season included a 4-0 loss Eintracht Frankfurt on Saturday.
"For this, Domenico and his coaching staff deserve our gratitude," Leipzig chief executive Oliver Mintzlaff said of the German Cup win. "However, after our mediocre start to the Bundesliga season with five points from five games, along with the recent defeats to Eintracht and Shakhtar, we believe that a change of management is the right course of action to turn things round quickly."
Leipzig's upcoming schedule includes hosting Borussia Dortmund in the Bundesliga on Saturday and a trip to defending champion Real Madrid in the Champions League next Wednesday.
Shakhtar came to Leipzig with a weakened squad after losing most of its overseas players following Russia's invasion of Ukraine, but the team scored from four of its five shots on goal.
Tedesco was hired by Leipzig nine months ago and previously coached Russian club Spartak Moscow for two years.
Leipzig did not immediately name an interim coach.