He attended Towanda High School, and graduated cum laude from Amherst College in 1915. He was a first lieutenant machine gunner in World War I, from 1917-1918. In 1925 he married Helen Ward Spencer.
He taught Latin in secondary schools in San Francisco, New York City, and Long Island through 1957. From 1957 to 1965, he taught at Amherst College.
He taught at many poetry and creative writing workshops, including the University of New Hampshire Writers' Conference and the University of Colorado Writers' Conference.
He was a mentor to many poets, including Theodore Roethke. Among his literary friendships were those with Louise Bogan, Edmund Wilson, and Elizabeth Bishop.
His work appeared in Harper's, The New Yorker,
His papers are held at Amherst College.
He is known for a notorious literary prank. Asked to contribute a piece to Poetry in 1939, he penned 39 lines containing an acrostic. The first letters of each line spelled out the message: "Nicholas Murray Butler is a horses ass." The editor printed an apology and Humphries was banned from the publication. The ban was lifted in 1941.