Guthrie left home at age 15 to travel the country by freight train. He carried with him his guitar and harmonica and became a welcome figure in the hobo and migrant camps of the Great Depression of the 1930s. Singing songs drawn from his own country heritage and writing others based on his experiences with the dispossessed, Guthrie became a musical spokesman for labour and populist sentiment. Such songs as “So Long (It's Been Good To Know Yuh),” “Hard Traveling,” “Blowing Down This Old Dusty Road,” “Union Maid,” and (inspired by John Steinbeck's The Grapes of Wrath) “Tom Joad” were gradually adopted by other performers and became part of the folk canon. Making his way to New York City, he joined Pete Seeger and others in the Almanac Singers, with whom he continued to perform for farmer and worker groups after serving in the Merchant Marine during World War II. Probably the most famous of his more than 1,000 songs, “This Land Is Your Land” was also one of his last and was taken up by the civil-rights movement of the 1960s.

The last years of his life were spent in a New York hospital fighting Huntington's chorea, a degenerative disease of the nervous system. At the time of his death Guthrie had already begun to assume legendary proportions as a folk figure. A film version of his autobiography Bound for Glory (1943) appeared in 1976, and in 1998 Billy Bragg (Bragg, Billy) and Wilco released the critically acclaimed Mermaid Avenue, a collection of previously unrecorded lyrics by Guthrie that they had set to music; Mermaid Avenue Vol. II followed in 2000. His son Arlo Guthrie (b. 1947) also achieved considerable success as a writer and singer of folk songs.