Cowley was born August 24, 1898, in Belsano, Cambria County, Pennsylvania, to William Cowley and Josephine Hutmacher. He grew up in the East Liberty neighborhood of Pittsburgh, where his father, William, was a homeopathic doctor. Cowley attended Shakespeare Street elementary school and in 1915 graduated from Peabody High School, where his boyhood friend Kenneth Burke was also a student. Cowley’s first published writing appeared in his high school newspaper.

He attended Harvard University, but his studies were interrupted when he joined the American Field Service during World War I to drive ambulances and munitions trucks for the French army. He returned to Harvard in 1919 and became editor of The Harvard Advocate. He graduated with a B.A. in 1920.

While in Paris, Cowley found himself drawn to the avant-garde sensibilities of Dada, and also, like many other intellectuals of the period, to Marxism and its attempts to demystify the socioeconomic and political conditions that had plunged Europe into a devastating war. He travelled frequently between Paris and Greenwich Village in New York, and through these intersecting social circles came into close proximity, though he never officially joined, with the U.S. Communist Party. In 1929, Cowley became an associate editor of the left-leaning magazine The New Republic, which he steered in “a resolutely communist direction” By the early 1930s, Cowley became increasingly involved in radical politics. In 1932, he joined Edmund Wilson, Mary Heaton Vorse, and Waldo Frank as union-sponsored observers of the miners’ strikes in Kentucky. Their lives were threatened by the mines’ owners, and Frank was badly beaten. When Exile’s Return was first published in 1934, it put forth a distinctly Marxist interpretation of history and social struggle.

Cowley married artist Peggy Baird; they were divorced in 1931. His second wife was Muriel Maurer. Together they had one son, Robert William Cowley, who is an editor and military historian.

In 1935, Cowley helped to establish a leftist collective, The League of American Writers. Other notable members included Archibald MacLeish, Upton Sinclair, Clifford Odets, Langston Hughes, Carl Sandburg, Carl Van Doren, Waldo Frank, David Ogden Stewart, John Dos Passos, Lillian Hellman, and Dashiell Hammett. Cowley was appointed Vice President, and over the next few years became involved in numerous campaigns, including attempts to persuade the United States government to support the Republicans in the Spanish Civil War. He resigned in 1940, owing to concerns that the organization was too heavily influenced by the Communist Party.

In 1941, near the outset of the United States’ involvement in World War II, President Franklin D. Roosevelt appointed Cowley’s associate, poet and “popular front” interventionist Archibald MacLeish, as head of the War Department’s Office of Facts and Figures (precursor to the Office of War Information). MacLeish recruited Cowley as an analyst. This decision resulted in anti-communist journalists such as Whittaker Chambers and Westbrook Pegler publicly exposing Cowley’s left-wing sympathies. Cowley soon found himself in the crosshairs of congressman Martin Dies (D-Tex.) and the House Un-American Activities Committee. Dies accused Cowley of belonging to seventy-two communist or communist-front organizations. This number was certainly an exaggeration, but Cowley had no recourse to deny it. MacLeish soon came under pressure from J. Edgar Hoover and the Federal Bureau of Investigation to dismiss Cowley. In January 1942, MacLeish sent his reply that the FBI needed a course of instruction in history. “Don’t you think it would be a good thing if all investigators could be made to understand that Liberalism is not only not a crime but actually the attitude of the President of the United States and the greater part of his Administration?”, he said. Nevertheless, Cowley resigned two months later, vowing to never write about politics again.

To the end, Cowley remained a humanitarian in the world of letters. He wrote writer Louise Bogan in 1941, “I’m almost getting pathologically tender-hearted. I have been caused so much pain by reviewers and political allrightniks of several shades of opinion that I don’t want to cause pain to anybody.”

In 1944, having been more or less silenced politically, Cowley began a career as a literary advisor, editor, and talent scout at Viking Press. He was hired to work on the Portable Library series, which had started in 1943 with As You Were: A Portable Library of American Prose and Poetry Assembled for Members of the Armed Forces and Merchant Marine. In its inception, the Portable Library was an anthology of paperback reprints that could be mass-produced cheaply and marketed to military personnel. It also emphasized an American literary tradition that could be construed as patriotic during wartime. Yet Cowley was able to steer the series toward what were, in his esteem, underappreciated writers.

The Portable Hemingway sold so well that Cowley was able to convince Viking to publish a Portable Faulkner in 1946. William Faulkner was, at the time, slipping into literary obscurity. By the 1930s, he was working as a Hollywood screenwriter and in danger of seeing his works go out of print. Cowley again argued for a dramatic revaluation of Faulkner’s position in American letters, enlisting him as an honorary member of the Lost Generation. Robert Penn Warren called The Portable Faulkner the “great watershed” moment for Faulkner’s reputation, and many scholars view Cowley’s essay as having resuscitated Faulkner’s career. Faulkner won a Nobel Prize in 1949. He later said, “I owe Malcolm Cowley the kind of debt no man could ever repay”.

Cowley then published a revised edition of Exile’s Return in 1951. The revisions downplayed some of the more overtly Marxist tenets, and more obviously emphasized the return of the exile as a necessary step toward reestablishing a nation’s solidarity: “the old pattern of alienation and reintegration, or departure and return, that is repeated in scores of European myths and continually re-embodied in life”, Cowley wrote. This time the book sold much better. Cowley also published a Portable Hawthorne (1948), The Literary Tradition (1954), and edited a new edition of Leaves of Grass (1959), by Walt Whitman. These were followed by Black Cargoes, A History of the Atlantic Slave Trade (1962), Fitzgerald and the Jazz Age (1966), Think Back on Us (1967), Collected Poems (1968), Lesson of the Masters (1971) and A Second Flowering (1973).

As an editorial consultant to Viking Press, he pushed for the publication of Jack Kerouac’s On the Road. Cowley’s work anthologizing 28 Fitzgerald short stories and editing a reissue of Tender Is the Night, restructured based on Fitzgerald’s notes, both in 1951, were key to reviving Fitzgerald’s reputation as well, and his introduction to Sherwood Anderson’s Winesburg, Ohio, written in the early 1960s, is said to have had a similar effect on Anderson’s reputation. Other works of literary and critical importance include Eight More Harvard Poets (1923), A Second Flowering: Works & Days of the Lost Generation (1973), And I Worked at the Writer’s Trade (1978), and The Dream of the Golden Mountains: Remembering the 1930s (1980). And I Worked won a 1980 U.S. National Book Award in the one-year category Autobiography.

When The Portable Malcolm Cowley (Donald Faulkner, editor) was published in 1990, the year after Cowley’s death, Michael Rogers wrote in Library Journal: “Though a respected name in hardcore literary circles, in general the late Cowley is one of the unsung heroes of 20th-century American literature. Poet, critic, Boswell of the Lost Generation of which he himself was a member, savior of Faulkner’s dwindling reputation, editor of Kerouac’s On the Road, discoverer of John Cheever, Cowley knew everybody and wrote about them with sharp insight. . . . . Cowley’s writings on the great books are as important as the books themselves . . . . All American literature collections should own this.”