Mr Ncube, who was in charge of the feared Central Intelligence Organisation, was a close ally of the 78-year-old president.
Mr Ncube becomes the fifth minister to be fired by President Mnangagwa since he came to power five years ago.
Zimbabwe President Emmerson Mnangagwa has fired his State Security Minister "for inappropriate conduct."
President Mnangagwa's office announced the sacking of Owen Ncube on Monday in a brief statement amid speculation that the two fell out over violence that rocked the ruling Zanu PF's recent internal elections.