The Pakistan Air Force (PAF) said that the French-made jet went down near Dera Ismail Khan town.
"Pakistan Air Force reports with regret that a PAF Mirage Aircraft, while on a routine operational training mission, crashed," PAF said in a statement.
Air Commodore Shafqat Mushtaq and Flight Lieutenant Sohaib Rasheed were killed in the crash.
A search and rescue operation is underway, while a board of inquiry has been ordered by Air Headquarters to determine the cause of accident.