From 1979 to 1992, Fleming hosted a daily radio talk show on KMOX in St. Louis. On Sunday evenings, he occasionally co-hosted Trivia Spectacular with David Strauss. He also hosted the syndicated radio program When Radio Was.
Fleming's acting career began at age four, when he starred in a Broadway play. His first television role was as a stunt double for Ralph Bellamy in the detective series Man Against Crime. He would later star in The Flying Tigers, The Californians, and International Detective.
Fleming also appeared in many television commercials. He was first spotted by legendary creator of TV shows Merv Griffin on a commercial for Trans World Airlines. Griffin thought Fleming was "authoritative, yet warm and interesting," and Fleming was invited to audition for the role of host in a new quiz show Griffin was developing. Fleming (an actor with no prior TV quiz show experience) was initially skeptical, but his agent encouraged him to "act like a game show host" at his audition and Fleming ultimately won the job. The show was Jeopardy!, which Fleming hosted from 1964 to 1975 and again from October 2,1978, to March 2,1979. As the first host of "the world's greatest quiz show," Fleming earned two Emmy Award nominations. While he was host of Jeopardy!, Fleming never missed a taping.
Because he hosted a quiz show, Fleming earned a reputation as being a storehouse of trivia. While appearing as a guest star on Hollywood Squares (another popular NBC game show in the 1960s and 1970s), Fleming was once selected as the "secret square." His question was, "In 1938, who won the Wimbledon women's tennis championship?" Fleming picked Helen Wills Moody, one of the three choices read to him. The female contestant (who had selected Fleming) turned to Hollywood Squares MC Peter Marshall and said, "Art Fleming would never lie! I agree!" He was right, and the contestant won $11,000. Fleming later said he didn't know a thing about tennis and had guessed the answer. He hoped the contestant would disagree, thinking he was wrong.
Throughout his career, Fleming starred in 5000 episodes of television programs and 48 motion pictures. After Jeopardy! was canceled in 1975, Fleming returned to acting. He played the role of W. Averell Harriman in the movie MacArthur and also appeared on episodes of Starsky and Hutch, Kingston: Confidential, and the TV miniseries The Moneychangers.
He also hosted a radio version of College Bowl for CBS. Fleming reprised his role as host of Jeopardy! in the movie Airplane II and in "Weird Al" Yankovic's music video "I Lost on Jeopardy". Fleming was also often called upon to host mock versions of Jeopardy! at trade shows and conventions.
Studio 25 of the NBC Burbank Studios is named in his honor.