Bickford was born in Cambridge, Massachusetts, during the first minute of 1891. The fifth of seven children, Charles was an intelligent but very independent and unruly child. He was tried and acquitted when he was only nine years old of the attempted murder of a motorist who had accidently driven over his dog. In his late teens he drifted aimlessly around the United States for a time but eventually graduated from the Massachusetts Institute of Technology.
Before breaking into acting, he worked as a lumberjack, investment promoter, and for a short time ran a pest extermination business. He eventually joined a road company and travelled throughout the United States for more than a decade where he appeared in various productions. During an appearance in a Broadway play called, "Outside Looking In," he was noticed by legendary filmmaker Cecil B. DeMille and offered a contract with MGM studios. He soon began working with MGM head Louis B. Mayer on a number of projects.
He became a star after playing Greta Garbo's lover in Anna Christie (1930), but never developed into a romantic lead. Always of independent mind, strong-willed and quick with his fists, Bickford would frequently argue and sometimes come to blows with Mayer.
During the production of DeMille's Dynamite, he punched out his director and eventually found himself blacklisted from MGM productions on several different occasions. Understandably, his association with MGM was short-lived, and Bickford became an independent actor for several years.
Later, he would sign with Twentieth Century Fox studios where it was anticipated he would play leading man roles. However, Bickford was mauled by a lion while filming East of Java in 1935. While he recovered from this attack, he would lose his contract with Fox as well as his leading man status due to extensive neck scaring coupled with his advancing age.