Fante's early years were spent in relative poverty. The son of an Italian born father, Nicola Fante, and an Italian-American mother, Mary Capolungo, Fante was educated in various Catholic schools in Boulder and Denver, Colorado, and briefly attended the University of Colorado.

In 1929, he dropped out of college and moved to Southern California to concentrate on his writing. He lived and worked in Wilmington, Long Beach, and in the Bunker Hill district of downtown Los Angeles, California.

He is known to be one of the first writers to portray the tough times faced by many writers in L.A. His work and style has influenced such similar authors as "Poet Laureate of Skid Row" Charles Bukowski and influential beat generation writer Jack Kerouac. He was proclaimed by Time Out magazine as one of America's "criminally neglected writers."