Marcelo Gallardo will leave River Plate when his contract ends in December after more than eight years at the club, he told reporters at a news conference on Thursday.
Gallardo, whose spell has marked one of the most successful periods in River's history, said he informed the club's board of his decision at a meeting on Wednesday.
"My contract ends in December and I will no longer be at the club. It is one of the most difficult and heartfelt decisions I have ever made," the Argentine said.
"Beyond the announcement, I am here to thank the people who trusted me," he added.
Gallardo arrived at River in May 2014 and won 14 titles with the Argentine club, including seven international trophies, six national cups and the 2021 Argentine league.
He also guided River to wins over bitter rivals Boca Juniors during the 2014 Copa Sudamericana and the Copa Libertadores in 2015, 2018 and 2019.
Gallardo's last match at River's iconic Estadio Monumental is against Rosario Central on Sunday before they play the last game of the season at Racing Club.
"I am going to finish my relationship as it should be, on Sunday I will have my last game at the Monumental," he added.
"Thank you [to the fans] for all the support and affection that you have shown me. It has been a beautiful story."
River are second in Argentina's top division, four points behind Boca Juniors, who have a game in hand.