Fadiman grew up in Brooklyn and was a nephew of the child prodigy William James Sidis The Prodigy Review - Bio: Life of William James Sidis. A graduate of Columbia University, he worked for Simon & Schuster for ten years, ending as its chief editor. He spent another ten years (1933—1943) in charge of The New Yorker's book review section and in 1944 became a judge for the Book of the Month Club. In the 1970s, Fadiman was also senior editor of Cricket Magazine, where he wrote Cricket's Bookshelf, a book review column for children.

His witticisms and sayings were frequently printed in newspapers and magazines. "When you reread a classic, you do not see more in the book than you did before, you see more in you than there was before", was one of the better known. Of Stendhal, Fadiman wrote, "He has no grace, little charm, less humor... [and] is not really a good storyteller..."

Books by Clifton Fadiman

• Reading I've Liked: Presented with an Informal Prologue and Various Commentaries (1941, British edition 1946)
• Party of One (1955)
• The American Treasury 1455-1955 (1955, ed.)
• Any Number Can Play (1957)
• Fantasia Mathematica (1958, ed.)
• Lifetime Reading Plan (1960, co-author)
• Enter, Conversing (1962)
• Mathematical Magpie (1962, ed.)
• Wally the Wordworm (1964)
• The World Treasury of Children's Literature (1984, ed.)
• The Little, Brown Book of Anecdotes (1985, ed.)
• The World of the Short Story: A 20th Century Collection (1986, ed.)
• Treasury of the Encyclopædia Britannica (1992, ed.)

Fadiman was already well known from radio where, from May 1938 until June 1948, he hosted its most popular quiz show, Information Please!. A trio of pundits...Clifton Fadiman, Franklin P. Adams, and John Kieran -- conducted each session with erudite charm and good-natured wordplay (guest John Gunther's mention of the then-current Iranian potentate prompted Fadiman to ask, "Are you shah?," to which Gunther quipped, "Sultanly."). Information Please! was briefly revived for CBS-TV in 1952 as a 13-week summer replacement for the musical variety program The Fred Waring Show. During that June—September period, devoted fans of the departed radio program could finally not only hear, but also see Fadiman, Adams, and Kieran in action. With the advent of TV, Fadiman gained in popularity, quickly establishing himself as an all-purpose, highly knowledgeable guest and host. At ease in front of the TV camera and experienced from his years in radio, he frequently appeared on talk shows and hosted a number of upscale quiz programs.

Fadiman was a prime example of the "witty intellectual" type popular on television in the 1950s. John Charles Daly, Bennett Cerf, George S. Kaufman, Alexander King and a number of other television celebrities personified, along with Fadiman, the highly educated, elegant, patrician raconteurs and pundits regarded by TV executives of that era as appealing to the upper-class owners of expensive early TV sets.

His longest-lasting TV program was This Is Show Business, which ran on CBS from July 15, 1949 to March 9, 1954. Called This Is Broadway during the first four months of its run, the show mixed song, dance and other musical entertainment, with information. Host Fadiman, celebrity guest panelists, and regular raconteurs/intellectuals Kaufman, Abe Burrows and Sam Levenson commented on the musical performers and chatted with them. In late September 1951, This Is Show Business became the first regular CBS series to be televised live from coast to coast. The continuing need in 1950s TV for summer series to replace live variety shows, likewise brought this show back in 1956 for a 12-week period (June 26-September 11). Fadiman and Burrows returned along with new panelists Walter Slezak and actress Jacqueline Susann, the future author of Valley of the Dolls. Susann's husband, TV executive Irving Mansfield, produced the 1956 revival for NBC.

Clifton Fadiman was also the last master of ceremonies to host the ABC-TV game show The Name's the Same. After the departure of original host Robert Q. Lewis. who had presided for three years, producers Mark Goodson and Bill Todman hired different hosts for the final 39-episode cycle: Dennis James for 18 weeks, then Bob and Ray for 10 weeks, and then Clifton Fadiman for the remaining 11 weeks. The series, broadcast live, featured namesakes of celebrities and other "famous names." On August 16, 1955, when a woman contestant was discovered to be "Hope Diamond," Fadiman personally orchestrated an astounding surprise: he arranged for the real Hope Diamond to be displayed to the amazed panelists and the national television audience. Such was Clifton Fadiman's reputation that the priceless jewel was entrusted to him.

Fadiman filled in for "What's My Line?" host John Charles Daly for two weeks in 1958 when Daly was on assignment in Tokyo.

Fadiman's first marriage was to Pauline Elizabeth Rush, with whom he had a son, Jonathan Rush.

His second marriage was to Annalee Jacoby (Annalee Whitmore Jacoby), aka Annalee Fadiman, an author and World War II foreign correspondent for Time and Life, who later used the name Annalee Jacoby Fadiman. Annalee was the co-author, with Theodore H. White of the famous book Thunder Out of China, published in 1946. They had a son, Kim Fadiman, and a daughter, editor Anne Fadiman. On 5 February 2002, Annalee committed suicide in Captiva, Florida, aged 85, after a long battle with breast cancer and Parkinson's disease. Milestones - TIME

Clifton Fadiman died on June 20, 1999 of pancreatic cancer on Sanibel Island, Florida at the age of 95. In the year of his death, Fadiman's Lifetime Reading Plan came back into print as The New Lifetime Reading Plan.