Reports late on Monday suggested that Hendon would be relieved of his duties after the O's were beaten 3-1 at home by Exeter City at the weekend.
That decision has now been confirmed via an official statement, with assistant manager Andy Hessenthaler taking control of the first team on an interim basis.
"The club can confirm that Ian Hendon has been relieved of his role as head coach of Leyton Orient. The club would like to thank Ian for his commitment and passion during his time at Leyton Orient and would like to wish him the best in his future endeavours," read a statement on the club's official website.
Hendon, 44, who has previously been in charge at both Barnet and Dover Athletic, took control of Orient at the end of last season following their relegation from League One.