Casey Stoney said she had made an "incredibly tough decision" after announcing she would step down as Manchester United Women head coach at the end of the season.
The former England international, 38, is leaving the post after three years in charge at United.
The first season, following the team's 2018 launch as a professional outfit, saw Stoney guide them to the Championship title.
United have subsequently recorded two fourth-placed finishes in the Women's Super League, ending up one point adrift of third-placed Arsenal this term as the Gunners won the race for a Champions League spot.
Stoney said in a statement on United's official website on Wednesday: "It has been an honour to lead the women's team at this great club and this has been an incredibly tough decision.
"Having come on board to start the team from scratch, then winning the Women's Championship in our first season, we have now successfully established the team as a force in the Women's Super League.
"I have loved leading this group and I am proud of what we have achieved together.
"However, after a difficult season with disruption caused by the pandemic, I now feel the time is right to take some time away and for someone else to come in and lead the team on the next stage of its journey.
"I want to thank the club, all of the fantastic staff, the fans, and most of all the players, for the incredible experience we have shared over the past three years."
United, who have had considerable injury problems this term, were unbeaten in their first 10 WSL games of the campaign and leading the table at the start of 2021 before slipping down the rankings.
Last week Stoney, a nominee for WSL manager of the season, said "not getting Champions League football for me is a personal failure".
The team's final match of 2020-21 is at home against Leicester in the FA Cup fifth round on Sunday. The latter stages of the competition will be completed next season.
United executive vice-chairman Ed Woodward said in Wednesday's statement: "Casey has been a driving force behind the success of our women's team since she joined the club in 2018.
"She has been an inspiration to her players and staff, to everyone at the club, and to the fans.
"Everyone at Manchester United thanks her for her unstinting hard work and dedication and pays tribute to her achievements. She will always be part of the Manchester United family."
John Murtough, United's football director, said: "Manchester United is completely committed to its women's team and to building on the legacy of Casey's achievements as we move forwards.
"With the recent historic first game at Old Trafford and the impact the team has made in the Women's Super League, the future is bright.
"While we will be sad to see Casey leave, the team and the operation will continue to go from strength to strength."
United said they were "in the process of recruiting a new women's head coach and this will be announced in due course."