In 1961, a group of civil rights activists known as the Freedom Riders began a desegregation campaign. The interracial group rode together on interstate buses headed south from Washington, D.C., and patronized the bus stations along the way to test the enforcement of Supreme Court decisions that prohibited discrimination in interstate passenger travel. Their efforts were unpopular with white Southerners who supported segregation. The group encountered early violence in South Carolina but continued their trip toward the planned destination of New Orleans.

On Mother's Day, May 14, 1961, a Greyhound bus carrying Freedom Riders arrived at the Anniston, Alabama, bus station shortly after 1 pm to find the building locked shut. Led by Ku Klux Klan leader William Chapel, a mob of 50 men armed with pipes, chains, and bats smashed windows, slashed tires, and dented the sides of the Riders' bus. Though warned hours earlier that a mob had gathered at the station, local police did not arrive until after the assault had begun.

Once the attack subsided, police pretended to escort the damaged bus to safety but instead abandoned it at the Anniston city limits. Soon after the police departed, another armed white mob surrounded the bus and began breaking windows. The Freedom Riders refused to exit the vehicle but received no aid from two watching highway patrolmen. When a member of the mob tossed a firebomb through a broken bus window, others in the mob attempted to trap the passengers inside the burning vehicle by barricading the door. They fled when the fuel tank began to explode. The Riders were able to escape the ensuing flames and smoke through the bus windows and main door, only to be attacked and beaten by the mob outside.

After police finally dispersed their attackers, the Freedom Riders received limited medical care. They were soon evacuated from Anniston in a convoy organized by Birmingham Civil Rights leader the Rev. Fred Shuttlesworth.