Karl Shapiro attended the University of Virginia before World War II, and immortalized it in a scathing poem called "University," which noted that "to hate the Negro and avoid the Jew is the curriculum." He did not return after his military service.

Karl Shapiro wrote poetry in the Pacific Theater while he served there during World War II. His collection V-Letter and Other Poems, written while Shapiro was stationed in New Guinea, was awarded the Pulitzer Prize for Poetry in 1945, while Shapiro was still in the military. Shapiro was American Poet Laureate in 1946 and 1947. (At the time this title was Consultant in Poetry to the Library of Congress which was changed by Congress in 1985 to Poet Laureate Consultant in Poetry to the Library of Congress.)

Poems from his earlier books display a mastery of formal verse with a modern sensibility that viewed such topics as automobiles, house flies, and drug stores as worthy of attention. Later work experimented with more open forms, beginning with The Bourgeois Poet (1964) and continuing with White-Haired Lover (1968). The influence of Walt Whitman, D. H. Lawrence, W. H. Auden and William Carlos Williams is evident in his work.

Shapiro's interest in formal verse and prosody led to his writing a long poem about the subjects, Essay on Rime (1945); A Bibliography of Modern Prosody (1948); and, with Robert Beum, A Prosody Handbook (1965; reissued 2006).

Selected Poems appeared in 1968, and Shapiro published one novel, Edsel (1971) and a three-part autobiography, "Poet" (1988-1990).

Shapiro edited the prestigious magazine, Poetry (see Poetry Magazine) for several years, and he was a professor of English at the University of Nebraska, Lincoln, where he edited Prairie Schooner, and at the University of California, Davis, from which he retired in the mid-1980s.

His other works include Person, Place and Thing (1942), (with Ernst Lert) the libretto to Hugo Weisgall's opera The Tenor (1950), To Abolish Children (1968), and The Old Horsefly (1993). Shapiro received the 1969 Bollingen Prize for Poetry, sharing the award that year with John Berryman.

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