In a statement reported by Syria's state news agency on Thursday, the ministry said Nawaf Fares had been "relieved of his duties" and should face "legal and disciplinary accountability."
Fares announced his defection in a video released on Wednesday, saying he was siding with "the revolution" against President Bashar Assad.
He is the highest profile diplomat to defect in the uprising and the second prominent figure to leave the regime in a week. Brig. Gen. Manaf Tlass, an Assad confidant and son of a former defense minister, fled Syria last week, though he has not spoken publically since.