The 34-year-old defenseman will become an unrestricted free agent and can sign with any team when NHL free agency begins July 28.
Yandle signed a seven-year contract with the Panthers on June 23, 2016, three days after he was acquired in a trade with the New York Rangers.
"We would like to extend a sincere thank you to Keith for all that he's contributed to the Florida Panthers organization and to the South Florida community over the past five seasons," Panthers general manager Bill Zito said. "While a decision of this kind is never an easy one to make, we believe that this shift is necessary as we look towards the 2021-22 season and our club's future."
Yandle missed his first game since March 22, 2009, with the Phoenix Coyotes, when Florida made him a healthy scratch for Game 3 of the Stanley Cup First Round against the Tampa Bay Lightning, ending his streak of 979 regular-season and Stanley Cup Playoff games that's two behind Coyotes forward Phil Kessel for the longest in NHL history.
"Extremely difficult," Panthers coach Joel Quenneville said May 21. "We've had a number of defensemen play probably comparable and those guys have been out. With 'Yands,' we're always aware of the situation in the regular season, but we made a decision to go with a different group.
"For the most part, the game was fine. But he handled it well. Not an easy decision to make and not easy for him, but he handled it like a great pro."
Yandle has played 922 consecutive regular-season games, the second-longest streak in NHL history behind Doug Jarvis (964), and had played 57 straight in the postseason. He scored 27 points (three goals, 24 assists) in 56 games this season, when he played his 1,000th NHL game March 7 against the Carolina Hurricanes.
Yandle has scored 600 points (102 goals, 498 assists) in 1,032 regular-season games for the Coyotes, Rangers and Panthers since entering the NHL in 2006-07, and 36 points (six goals, 30 assists) in 58 playoff games.
The Panthers have several young defensemen who were pushing Yandle for playing time. One of them was Gustav Forsling, who signed a three-year contract with Florida on Thursday.
The 25-year-old could have become a restricted free agent July 28. He scored NHL career highs in goals (five), assists (12) and points (17) in 43 regular-season games.
"After joining the Panthers in January, Gustav had a career season setting personal records and establishing his defensive game to bolster our blue line," Zito said. "We are looking forward to watching him continue to develop his game with our club."
NHL.com senior writer Dan Rosen contributed to this report
