Scholes has walked away from Boundary Park over claims of broken promises from his hometown team.
The 44-year-old took charge at Oldham last month and won his first match, but the ex-England midfielder failed to pick up another victory in his next six games and leaves with the side languishing in 14th place.
“It is with great regret that I have decided to leave the club with immediate effect,” Scholes said in a statement.
“I hoped to at the very least, see out my initial term of 18 months as the manager of a club I’ve supported all my life. The fans, players, my friends and family all knew how proud and excited I was to take this role.
“In the short period since I took on the role it unfortunately became clear that I would not be able to operate as I intended and was led to believe prior to taking on the role.
“I wish the fans, the players and the staff – who have been tremendous – all the best for the rest of the season and will continue to watch and support the club as a fan.”
Scholes, who won Premier League and Champions League titles during a glittering playing career with United, was appointed as Oldham boss on a one-and-a-half-year deal on February 11.
He resigned as a club director at non-league Salford, while retaining his 10 percent stake, before taking the job.