Mead's best known book has no plot; it is a satire of an instructional manual, very similar in form and subject matter to Stephen Potter's Gamesmanship. Mead's book was inspired by his corporate experiences; How to Succeed satirized contemporary office life in the United States in the guise of a self-help book. Its subtitle was "The dastard's guide to fame and fortune."

The book was a best-seller, and in 1961 it was adapted into a musical by Frank Loesser, with book by Abe Burrows. The stage musical, written by Abe Burrows and Frank Loesser with minor input by others, the play differs significantly from the book. It satirizes Mead's own career by depicting the rise of eager young J. Pierrepont Finch ... a window-washer who joins a huge corporation by starting in the mail room, and becomes chairman of the board a week later. The play starred Robert Morse as the young striver J. Pierrepont Finch and Rudy Vallee as the company president J.W. Biggley.

The play was a smash hit, with a Broadway run of 1,417 performances between October 1961 and March 1965. It won eight Tony Awards and the 1962 Pulitzer Prize for best drama. It was adapted into a movie, also starring Morse and several other members of the Broadway cast, in 1967. It was successfully revived on Broadway in 1995, starring Matthew Broderick as Finch.

"Not even computers will replace committees, because committees buy computers."

--Shepherd Mead, quoted in the Wall Street Journal, June 18, 1964.