Emma Hayes, Australia star striker Sam Kerr's manager at Chelsea, will leave the defending Women's Super League champions at the end of the season, the club said.
Hayes, who has won 14 major trophies at Chelsea, including six WSL titles, has been reported as being lined up to take over the United States national team.
Chelsea said she was leaving to "pursue a new opportunity outside of the WSL and club football".
She was immediately linked with a move to four-time women's world champion United States, following the resignation of coach Vlatko Andonovski in August.
In 11 years with Chelsea, Hayes has dominated, leading the team to two domestic league and cup doubles and one trophy treble.
She signed the prolific Kerr in 2020 from Chicago Red Stars.
"Emma has been one of the biggest drivers of change in women's football. Her achievements at Chelsea are unrivalled and will live in the club's history forever," co-sporting directors Laurence Stewart and Paul Winstanley said in a statement.
"Given everything she has contributed to Chelsea in over a decade with the club, and the legacy she leaves behind, we would never stand in her way when she felt it was the right time to pursue a new challenge."
The United States had a disappointing World Cup in Australia and New Zealand in July and August.
Aiming to become the first nation to win the trophy three times in a row, they were eliminated by Sweden in a penalty shootout in the round of 16. Andonovski left shortly after.
Hayes has worked in America in the past as a coach with Long Island Lady Riders, Iona College and Chicago Red Stars.
She has been at Chelsea since 2012 and will have the chance to win a seventh WSL title before she departs.
Chelsea moved to the top of the table with Saturday's 6-0 win at Aston Villa, though Hayes opted to rest Kerr, who remained on the bench throughout.