Kirkaldy was born on April 9, 1917, in Baltimore, Maryland. On a July morning in 1944, Kirkaldy, recovering from a miscarriage, boarded a Greyhound bus in Gloucester, Virginia, to return to her home in Baltimore. She selected a seat in a section of the back of the bus designated for black passengers. A half hour into the trip, a white couple boarded the crowded bus and the bus driver, under authority given to him by Jim Crow laws and segregation practices, demanded that Kirkaldy give up her seat. Raised by a religious family that discouraged questioning authority, Kirkaldy decided that her rights outweighed her obedience and she refused to give up her seat. The bus driver drove directly to a local jail and a sheriff's deputy boarded the bus and handed her a warrant for her arrest. Kirkaldy tore up the warrant and kicked the officer when he tried to grab her.

Kirkaldy's stand against discrimination and segregation landed her in jail. Kirkaldy and her lawyer, Spottswood Robinson III, decided to plead guilty to the charge of resisting arrest but not guilty to violating the Virginia segregation law. Robinson argued that the segregation law violated the interstate commerce clause of the U.S. Constitution. Kirkaldy lost her case, but with the help of the NAACP and Thurgood Marshall, it was brought before the U.S. Supreme Court.

Justices heard arguments in Irene Morgan v. Commonwealth of Virginia, and handed down a landmark decision for Civil Rights. On June 3, 1946, they agreed that segregation violated the Constitution's protection of interstate commerce. This decision gave a serious blow to segregation laws and the South refused to enforce the ruling. In response, a group of civil rights activists rode buses and trains across states in the South in 1947, named the Journey of Reconciliation. The activists immortalized Kirkaldy in their rally song, "You Don't Have to Ride Jim Crow," singing "Get on the bus, sit anyplace, 'Cause Irene Morgan won her case."

Irene Morgan v. Commonwealth of Virginia served as a catalyst for further court rulings and the Civil Rights movement as a whole. Eight years later, the Supreme Court decided in Brown v. Board of Education that segregation violated Equal Rights Protection as stated in the 14th Amendment. In 1955, Rosa Parks followed Kirkaldy's example, and famously refused to give up her bus seat in Montgomery, Alabama.

For her actions, Kirkaldy received numerous awards, including the Presidential Citizens Medal, the second highest civilian award in the country. Kirkaldy died on August 10, 2007. Her act of courage served as a vehicle of change for the betterment of African Americans throughout the United States.