Floyd was born in Georgia but grew up in Oklahoma, spending considerable time in nearby Kansas, Arkansas and Missouri. He got his start in crime at age 18 when he stole $3.50 in pennies from a local post office, according to an issue of Time magazine, published 22 October 1932. Three years later he was arrested for a payroll robbery, September 16, 1925, in St. Louis, Missouri and served five years in prison.

When paroled, Floyd vowed that he would never see the inside of another prison. Entering into partnerships with more established criminals in the Kansas City underworld, he committed a series of bank robberies over the next several years; it was during this period that he acquired the nickname "Pretty Boy." According to one account, when the payroll master targeted in a robbery described the three perpetrators to the police, he referred to Floyd as "a mere boy — a pretty boy with apple cheeks." (Other accounts claim the nickname was bestowed by a woman as a compliment.) Like his contemporary Baby Face Nelson, Floyd hated his nickname.

In 1929, he faced numerous arrests. On March 9, he was arrested in Kansas City on investigation and again on May 6 for vagrancy and suspicion of highway robbery, but was released the next day. Two days later, he was arrested in Pueblo, Colorado, charged with vagrancy. He was fined $50.00 and sentenced to 60 days in jail.[citation needed]

In November 1929, he traveled to Oklahoma for his father's funeral. His father had been killed by a neighbor, Jim Mills, who was acquitted but "vanished".[citation needed]

One of the members of Floyd's gang, "Frank Mitchell" was arrested in Akron, Ohio on March 8, 1930, charged in the investigation of the murder of an Akron police officer, who had been killed during a robbery that evening.

The law next caught up with Floyd in Toledo, Ohio where he was arrested on suspicion on May 20, 1930; he was sentenced on November 24, 1930 to 12–15 years in Ohio State penitentiary for the Sylvania Ohio Bank Robbery but he escaped.[citation needed]

Floyd was a suspect in the deaths of bootlegging brothers Wally and Boll Ash of Kansas City. They were found dead in a burning car on March 25, 1931. A month later on April 23, members of his gang killed Patrolman R. H. Castner of Bowling Green, Ohio, and on July 22 Floyd himself killed ATF Agent C. Burke in Kansas City, Missouri.

In 1932, former sheriff Erv Kelley of McIntosh County, Oklahoma, tried to ambush/arrest Floyd; he was killed on April 7. In November of that year, three members of Floyd's gang attempted to rob the Farmers and Merchants Bank in Boley, Oklahoma.

Floyd and Adam Richetti became the primary suspects in a June 17, 1933 gunfight known as the "Kansas City Massacre" that resulted in the deaths of four law officers. Though J. Edgar Hoover used the incident as ammunition to further empower the FBI to pursue Floyd, historians are divided as to whether or not he was involved.

The gunfight was the result of an attempt by Vernon Miller and accomplices to either free or silence recaptured bank robber Frank "Jelly" Nash at the Union Railway Station in Kansas City, Missouri. As lawmen escorted Nash to a car, bandits emerged from hiding and opened fire. Two Kansas City detectives, one Oklahoma City police chief named Otto Reed, and FBI Special Agent Ray Caffrey were killed. Nash was killed as well, while sitting in the car. Two other Kansas City police officers survived by slumping forward in the backseat and feigning death. As the gunmen inspected the car, another officer responded from the station and fired at them, forcing them to flee. Miller was found dead on November 27, 1933, outside Detroit, Michigan, beaten and strangled.