The veteran striker joined the Foxes from non-league Fleetwood Town back in 2012 and played an instrumental role in the club's fairytale Premier League title win in 2016.
Vardy, 38, has scored 198 goals in 498 appearances for Leicester and was also part of the team that won the FA Cup in 2021 but will leave following a disappointing season that has seen the Foxes immediately relegated back to the Championship after returning to the top-flight last year.
In a video posted by the club, the former England international said: "To the fans of Leicester, I'm gutted that this day is coming, but I knew it was going to come eventually.
"I've spent 13 unbelievable years at this club, with lots of success, and some downs, but the majority have all been highs.
"It's finally time to call it a day, which I'm devastated about it, but I think the timing is right."
Vardy scored 24 times as Leicester won the Premier League in the 2015-16 season and is the last remaining player from the remarkable triumph still at the King Power Stadium.
He later became the oldest player to win the Premier League's Golden Boot when he hit 23 goals in the 2019-20 campaign at the age of 33.
Vardy has no plans to retire from football and is thought to have interest from Major League Soccer (MLS) clubs in the United States.
He said: "I want to keep playing and doing what I enjoy doing most, scoring goals. Hopefully there is one or two more for Leicester between now and the end of the season, and many more in the future. I might be 38 but I’ve still got the desire and ambition to achieve so much more."
Leicester chairman Aiyawatt Srivaddhanaprabha added: "Jamie is unique. He is a special player and an even more special person. He holds a place in the hearts of everyone connected to Leicester City, and he certainly has my deepest respect and affection. I am endlessly grateful for everything he has given to this football club."