Unable to stay in Memphis after the loss of her family Mary returned to Chicago where she established a dressmaking business. Bad luck continued to haunt her her for in 1871 the Great Fire of Chicago destroyed her home and business leaving her homeless and penniless. Alone and desperate she turned to her deceased husband's fellow union members for help. The kindness extended to her by the union workers was in start contrast to the indifference shown by her wealthy employers for the wretched homeless and poor souls who aimlessly wandered the streets in search of employment or food to feed their families.
In her biography she expressed her revulsion to such wanton indifference when recalling earlier experiences. Often while sewing for the lords and barons who lived in magnificent houses on the Lake Shore Drive, I would look out of the plate glass windows and see the poor, shivering wretches, jobless and hungry, walking alongside the frozen lake front. The contrast of their condition with that of the tropical comfort of the people for whom I sewed was painful to me.” My employers seemed neither to notice nor to care".
The compassion of the exploited in contrast to the callousness and indifference of the exploiters galvanized Marys' resolve to dedicate the rest of her life to the pursuit of a better life and working conditions for the ordinary working man, woman and child.
For the next number of years Mary made Chicago her base as she traveled from industrial area to industrial area working as a union activist with the Knights of Labor whose purpose was "to unite all workers under a single organization". She had a real talent for inspiring others with her speeches. During critical periods in labor strikes she would convince workers to stay the course when the management brought in strike-breakers and militias.
In 1873, during a coal miners strike in Pennsylvania she came face to face with Irish coal miners many of whom were veterans of the Civil War. The conditions she witnessed bordered on slavery with women and children near starvation. It was her efforts on their behalf coupled with her concern for their welfare that earned her the nickname "Mother Jones."
Mary continued to travel the country in support of striking workers. In 1877 she was involved in the nationwide walkout for better conditions by railroad workers. In 1880 she was in Chicago on behalf of workers trying to obtain an eight-hour day. She also took part in the strike at the McCormick-Harvester works, where a bomb killed several policemen. The police retaliated by firing randomly into a crowd of union workers, killing 11 and wounding dozens of others.
Apart from her involvement as an organizer and educator in striker tactics she gained prominence for organizing the wives and children of striking workers in demonstrations on their behalf. She became known as "the most dangerous woman in America," a phrase coined by a West Virginia district attorney, Reese Blizzard, in 1902, at her trial for ignoring an injunction banning meetings by striking miners. According to Clarence Darrow, she was "one of the most forceful and picturesque figures of the American labor movement".
One of her best-known activities was leading a march of miners' wives "who routed strikebreakers with brooms and mops in the Pennsylvania coalfields in 1902.". Another was leading the "children's crusade," a caravan of striking children from the textile mills of Kensington, Pennsylvania, to President Theodore Roosevelt's home in Long Island, New York, in 1903, to dramatize the case for abolishing child labor.
In her later years she was arrested during a violent strike in West Virginia and sentenced to 20 years in jail. Public outcry was so loud that she was pardoned by the governor and released. In 1913 she participated in the yearlong strike by miners in Colorado. She was arrested and imprisoned twice for a total of three months for trespassing on the mine owners property. After the "machine-gun massacre" of miners and their families in a tent colony at Ludlow, Colorado, on April 20, 1914, when 20 people were killed, she traveled the country informing the public as to what happened. As a result of her efforts the government of Woodrow Wilson was forced to intervene forcing the union and the owners to agree to a truce and create a grievance committee at each mine.