The 49-year-old former Gillingham boss has agreed a two-year deal to become Ian Hendon’s number two at Brisbane Road.
O’s chief Hendon told the club website: “I am delighted to have someone with Andy’s experience and knowledge by my side.
“I have worked with him and he is a very good coach. I also played alongside Andy in the same team and know what attributes he will bring to the club.
“Andy will work alongside Kevin Nugent, who remains very much part of my coaching team.”
Hessenthaler, who leaves his position as number two at Priestfield, added on Gillingham’s official site: “This was an incredibly difficult decision as I’ve had a 20-year relationship with Gillingham and I love the football club.
“However I felt it’s a fresh challenge for me, I’ll be working with Ian again who I’ve spent time with in the past and I look forward to what lies ahead.
“That said I’m disappointed to be cutting short my working relationship with Justin (Edinburgh). He’s been fantastic since he walked through the door and he’s definitely the right person to take this club forward.
“We’ve become close friends and I wish him, and everybody at the club, the very best of luck.”