The 52-year-old, who only arrived in Genoa last December, is expected to be succeeded by either Sinisa Mihajlovic or Zdenek Zeman.
Sunday night's 2-1 defeat at Fiorentina left the Blucerchiati 18th in Serie A, just three points above bottom-placed Sassuolo.
Samp president Edoardo Garrone called an emergency meeting Monday and, after seven hours of talks, the decision was taken to part company with Rossi and his backroom team.
"The club thanks everyone for their work and the professionalism that they have shown in these months working together and wishes everyone the best in their respective careers," read a statement released by the club.
The 52-year-old Rossi, who only arrived at the Luigi Ferraris last December, is expected to be replaced at the helm by either former defender Sinisa Mihajlovic, who is currently in charge of Serbia, or ex-Roma boss Zdenek Zeman.