Mary Jane Jackson was born in 1836 on Girod Street in New Orleans, Louisiana. She entered the world of prostitution at the age of 13 and, by 14, became the mistress of a local saloon owner. After their relationship ended when she was 17, Jackson assaulted him severely, resulting in his hospitalization with a broken nose and a severed ear. Following this incident, she moved between various brothels, often clashing with other prostitutes due to her volatile temperament. ​

Jackson's violent tendencies escalated over the years. In 1856, at the age of 20, she committed her first known murder by beating a man to death after he insulted her. The following year, she fatally stabbed a nearly seven-foot-tall man known as "Long Charley." On November 7, 1859, Jackson, accompanied by two women, Ellen Collins and America Williams, visited a saloon on Rampart Street. After a confrontation with a blacksmith named Laurent Fleury, who had asked her to stop cursing, Jackson and her companions stabbed him to death. Although she was arrested and found in possession of Fleury's belongings, she was released due to inconclusive autopsy results. ​

While incarcerated, Jackson became involved with John Miller, a jailer and fight manager with a criminal background. After her release, they engaged in robberies together in the French Quarter. On December 5, 1861, following a domestic dispute, Jackson fatally stabbed Miller. She was convicted of manslaughter and sentenced to ten years in prison. However, due to the American Civil War and the intervention of military governor George F. Shepley, she was released after serving only nine months. After her release in 1862, Jackson left New Orleans, and her whereabouts became unknown. ​