Darren Sarll leaves the club just hours after their FA Cup exit at the hands of National League North side Brackley Town.
The Pools are 16th in the National League and have just one win in their last seven games in all competitions - but did win their last league outing - a 4-3 win against Sutton United.
Former Woking boss Sarll joined in the summer but leaves after 15 games in charge.
Lennie Lawrence will take temporary control of the team until a new manager is announced.
"Hartlepool United’s Board can confirm that they have today parted company with Manager Darren Sarll." a club statement read.
"Lennie Lawrence will take over manager duties in the interim supported by the existing football staff.
"A further update will follow in due course."