The 55-year-old Italian has been sacked after five years at the Petrovsky Stadium and will be replaced by former midfielder Sergei SemakZenit St Petersburg has sacked coach Luciano Spalletti after five years with the Russian club.
The Italian had led the club to the 2010 and 2011-12 Russian Premier League titles, but Zenit's domestic hegemony ended last term when CSKA Moscow won the title.
Zenit is currently two points off Lokomotiv Moscow in the table and on the brink of Champions League elimination following a 4-2 home loss in the last 16 to Borussia Dortmund.
A 0-0 home draw with Tom Tomsk on Sunday proved to be the final straw, with the club deciding to fire the former Roma coach.
Former Zenit midfielder Sergei Semak will take charge of the side until the end of the season, having only ended his playing career last year.
The 38-year-old, who won 65 caps for Russia, also represented the likes of CSKA, Paris Saint-Germain and Rubin Kazan.