The former Gillingham boss becomes the first managerial departure in the Football League this term following a three-match winless streak that left Orient 14th in Sky Bet League Two with three wins from nine games.
The 51-year-old, who signed a one-year deal during the summer, took over from former player-manager Kevin Nolan for the final five games of the 2015-16 campaign.
Despite a positive start to the season which saw Orient climb as high as fourth earlier in the month, chairman Francesco Becchetti has made Hessenthaler his seventh managerial casualty in two years at the Matchroom Stadium following successive defeats to Yeovil and Notts County.
A statement on the club's website read: "The club can confirm that Andy Hessenthaler has been relieved of his role as first team manager.
"We would like to thank Andy for his service to Leyton Orient since arriving in July 2015 and wish him well in his future career.
"Assistant manager Andy Edwards will be assuming Hessenthaler's duties on an interim basis and will take charge of the team for tomorrow's night's Sky Bet League Two home game with Plymouth Argyle."
Source : PA
Source: PA