Clyde Chestnut Barrow was born in Ellis County, Texas, near Telico, a town just south of Dallas. He was the fifth of seven children of Henry Basil Barrow (1874–1957) and Cumie T. Walker (1874–1943), a poor farming family that emigrated, piecemeal, to Dallas in the early 1920s as part of a wave of resettlement from the impoverished nearby farms to the urban slum known as West Dallas.

Clyde was first arrested in late 1926, after running when police confronted him over a rental car he had failed to return on time. His second arrest, with brother Marvin "Buck" Barrow, came soon after, this time for possession of stolen goods (turkeys). Despite having legitimate jobs during the period 1927 through 1929, he also cracked safes, robbed stores, and stole cars. After sequential arrests in 1928 and 1929, he was sent to Eastham Prison Farm in April 1930. While in prison, Barrow beat to death another inmate who had repeatedly assaulted him sexually. It was Clyde Barrow's first killing.