Bickford had intended to attend the Massachusetts Institute of Technology (MIT) to earn an engineering degree, but while wandering around the country, he became friends with the manager of a burlesque show, who convinced Bickford to take a role in the show. He debuted in Oakland, California, in 1911. Bickford enjoyed himself so much that he abandoned his plans to attend MIT. He made his legitimate stage debut with the John Craig Stock Company at the Castle Square Theatre in Boston in 1912. He eventually joined a road company and traveled throughout the United States for more than a decade, appearing in various productions. In 1925, while working in a Broadway play called "Outside Looking In", co-star James Cagney (in his first Broadway role) and he received rave reviews. He was offered a role in Herbert Brenon's 1926 film of "Beau Geste", but anxious not to give up his newfound Broadway stardom, turned it down, a decision he later came to regret. Following his appearance in the critically praised but unsuccessful Maxwell Anderson-Harold Hickerson drama about the Sacco and Vanzetti case, "Gods of the Lightning" (Bickford was the Sacco character), Bickford was contacted by filmmaker Cecil B. DeMille and offered a contract with Metro-Goldwyn-Mayer (MGM) studios to star in DeMille's first talking picture, "Dynamite". He soon began working with MGM studio head Louis B. Mayer on a number of projects.