Skinner spent five years with the club, leading them to Women’s FA Cup success in 2024 to secure their first major honour.
Manchester United also finished second in the WSL in 2023, their highest domestic finish, and reached the group stages of the Women’s Champions League for the first time last year.
The 43-year-old’s departure comes by mutual agreement with Manchester United set to open their season with a trip to London City Lionesses on 4 September.
“Marc leaves having made a significant contribution to the continued progress of Manchester United Women,” a statement said. “The club places on record its sincere thanks for his professionalism, commitment and dedication throughout his time at United, and wishes him every success in the future.”
Manchester United finished fourth in the WSL last season.
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