Wolfe was educated at Yale University, and worked in the United States Merchant Marine during the 1930s; in 1937 he served briefly as secretary to Leon Trotsky during the latter's exile in Mexico. During World War II he was employed as a military correspondent by a number of science magazines, and then in 1946 he began to write fiction. Wolfe was the co-writer of musician Milton Mezzrow's autobiography Really the Blues.
He wrote several novels, and plays, mostly for television, but is known primarily for his 1952 science-fiction novel Limbo. Because Limbo was set in the then-distant future of 1990, the original British edition is titled Limbo '90. The publisher claimed that Wolfe had written "the first book of science-fiction to project the present-day concept of 'cybernetics' to its logical conclusion".David Pringle selected Limbo for inclusion in his book Science Fiction: The 100 Best Novels.J.G. Ballard praised Wolfe's "lucid intelligence" and claimed Limbo helped encourage him to start writing fiction. Boucher and McComas, however, received the novel poorly, calling it "pretentious hodgepodge" and describing its theme as "a symbolically interesting idea . . . never developed with consistent or convincing details."P. Schuyler Miller gave Limbo a mixed review, describing it as a "colossus of a novel" while faulting its "endless talk."