Whittingham initially took the reins at Fratton Park on a caretaker basis last November, but penned a one-year rolling deal in April when the club came out of administration.
Hampered by a 10-point deduction, the 49-year-old was unable to prevent relegation from League One last term and has now been relieved of his duties with Portsmouth sitting 18th in English football's fourth tier.
A statement on Portsmouth's official website read: "Portsmouth Community Football Club regret to announce that, following a meeting with the chairman, CEO and finance director, Guy Whittingham has today left his post as manager after his contract was terminated.
"The club wishes to place on record its sincere gratitude to Guy for his service to the club during difficult times.
"Andy Awford (Portsmouth's academy manager) has been put in caretaker charge, assisted by (first-team coach) Alan McLoughlin and (striker) David Connolly."
