The 11-year league veteran and U.S. women's national team standout will play her final regular-season match at Seattle's Lumen Field on Oct. 6 against the Washington Spirit.
Rapinoe, 38, is preparing to compete with the two-time defending champion USWNT in the 2023 FIFA Women's World Cup, which runs from July 20 to Aug. 20 in New Zealand and Australia.
Rapinoe also confirmed Saturday that this will be her final World Cup.
"I've been able to have such an incredible career, and this game has brought me all over the world and allowed me to meet so many amazing people," Rapinoe said in a statement to U.S. Soccer.
"I feel incredibly grateful to have played as long as I have, to be as successful as we've been, and to have been a part of a generation of players who undoubtedly left the game better than they found it. To be able to play one last World Cup and one last NWSL season and go out on my own terms is incredibly special."
Rapinoe joined the OL Reign during the NWSL's inaugural season in 2013 and holds the club records for goals (48) and assists (25) in 109 matches.
She has won three NWSL Shields with the Reign and earned one Best XI and two Second XI selections. She is also the league's all-time leader with 13 penalty kick goals.
Internationally, Rapinoe has earned 199 caps and a 2012 Olympic gold medal along with the World Cup victories in 2015 and 2019. In 2019, she was named Best FIFA Women's Player and won the Ballon d'Or Feminin.
Rapinoe has 63 goals and 73 assists with the USWNT while compiling a record of 157-14-28.
"I want to thank my family for being by my side all these years," Rapinoe added. "Thanks to all my teammates and coaches all the way back to my first days in Redding, on to college at the University of Portland and of course thanks to U.S. Soccer, the Seattle Reign and especially Sue [Bird], for everything.
"I will forever cherish the friendships and support over the years in this game, and I am beyond excited for one last ride with the National Team and the Reign."
"She's so key for this team on and off the field," USWNT left back Crystal Dunn said. "I did tell her at the beginning of this year that I have no idea if this is your last one, but I'm going to do whatever it takes to get myself into a place where I can help this team win. And obviously send her off the way that she deserves, which is the queen that she is."
An outspoken advocate for equal pay in women's soccer and supporter of LGBTQ+ rights, President Joe Biden last year awarded Rapinoe the Presidential Medal of Freedom, the nation's highest civilian honor.
"Pino's always just been a huge advocate for this team. She's been a backbone of this team. And so whether it's going through the equal pay fight, going through standing up for marginalized communities and backgrounds, she's someone who is going to stand up for that when it's not always a popular opinion," USWNT captain Alex Morgan said.
Information from Reuters and The Associated Press was included in this report.