The Sports’ inconsistency has proved costly as the club acted immediately after Saturday’s defeat at Billericay Town.
It was Eastbourne’s fourth National League South loss in a row.
Defeat in Essex in Saturday followed set-backs against struggling Truro City, East Thurrock and also against Welling United.
They begun 2019 strongly but their form has taken a dip since beating Dulwich Hamlet and Chippenham at the turn of the year.
In a season which held ambitions of a push for the play-offs, the south coast club now find themselves in 15th place.
Howell had been in charge since May 2017 after joining the club a day after taking Bognor Regis Town to promotion.
Eastbourne have confirmed the departure in a short statement on their website.
They say more details will be made public in due course as they begin their search for a new manager.