The 74-year-old Wallace made the surprising announcement in the closing moments of "Fox News Sunday" on Dec. 12.
"Finally, a personal note," Wallace said. "After 18 years, this is my final 'Fox News Sunday.' It is the last time, and I say this with real sadness, we will meet like this.
"Eighteen years ago, the bosses here at Fox promised me they would never interfere with a guest I booked or a question I asked, and they kept that promise. I have been free to report to the best of my ability, to cover the stories I think are important, to hold our country's leaders to account. It's been a great ride."
At Fox, Wallace covered five presidential elections and interviewed every president since George H.W. Bush. In addition, he recently performed sitdown interviews with world leaders such as France's Emmanuel Macron and Russia's Vladimir Putin.
He became the first Fox News journalist to moderate a presidential debate during the 2016 race between Donald Trump and Hillary Clinton.
"And, I've gotten to spend Sunday mornings with you," Wallace said. "It may sound corny, but I feel we've built a community here. There's a lot you can do Sunday mornings. The fact you've chosen to spend this hour with us, is something I cherish."
Wallace said he is moving on to a "new adventure," that will allow him to "go beyond politics" and allow him to focus on "all the things I'm interested in."
Wallace did not disclose where he will be appearing after Fox News, or when.
"I hope you'll check it out," he said. "And so, for the last time dear friends, that's it for today. Have a great week, and I hope you'll keep watching 'Fox News Sunday.' "
Fox News has not yet commented on Wallace's announcement, or who will be hosting the show next Sunday.
A Harvard graduate and the son of the late "60 Minutes" journalist Mike Wallace, Chris Wallace worked at the Boston Globe, ABC News, and NBC News before joining Fox News in 2003.
He was ranked as being one of the most trusted TV news anchors in America in a recent poll.
Click here to follow Daily Voice Greenwich and receive free news updates.