He led the team for the final five games of the season as the O's finished eighth, after being assistant to both Ian Hendon and Kevin Nolan.
The 50-year-old former Gillingham and Dover boss won three and lost two during his spell in temporary charge.
A statement said his "expertise, spirit and passion" secured him the role.
Hessenthaler is the seventh different man to take charge of the side since Italian businessman Francesco Becchetti bought the O's in the summer of 2014.
Leyton Orient have appointed Andy Hessenthaler as their full-time manager on a one-year contract after his stint in charge as caretaker boss.