Mary Mallon was born in 1869 in Cookstown, County Tyrone, in what is now Northern Ireland. She emigrated to the United States in 1883 at the age of 15. She lived with her aunt and uncle for a time and later found work as a cook for affluent families.

From 1900 to 1907, Mallon worked as a cook in the New York City area for seven families. In 1900, she worked in Mamaroneck, New York, where, within two weeks of her employment, residents developed typhoid fever. In 1901, she moved to Manhattan, where members of the family for whom she worked developed fevers and diarrhea, and the laundress died. Mallon then went to work for a lawyer; she left after seven of the eight people in that household became ill.

In 1906, she took a position in Oyster Bay, Long Island, and within two weeks 10 of the 11 family members were hospitalized with typhoid. She changed jobs again, and similar occurrences happened in three more households. She worked as a cook for the family of a wealthy New York banker, Charles Henry Warren. When the Warrens rented a house in Oyster Bay for the summer of 1906, Mallon went along too. From August 27 to September 3, six of the 11 people in the family came down with typhoid fever. The disease at that time was "unusual" in Oyster Bay, according to three medical doctors who practiced there. Mallon was subsequently hired by other families, and outbreaks followed her.

In late 1906, one family hired a typhoid researcher named George Soper to investigate. Soper published the results on June 15, 1907, in the Journal of the American Medical Association. He believed Mallon might be the source of the outbreak. He wrote:

Mallon attracted so much media attention that she was called "Typhoid Mary" in a 1908 issue of the Journal of the American Medical Association. Later, in a textbook that defined typhoid fever, she was again called "Typhoid Mary."

Eventually, Eugene H. Porter, the New York State Commissioner of Health, decided that disease carriers should no longer be kept in isolation and that Mallon could be freed if she agreed to stop working as a cook and take reasonable steps to prevent transmitting typhoid to others. On February 19, 1910, Mallon agreed that she was "prepared to change her occupation (that of a cook), and would give assurance by affidavit that she would upon her release take such hygienic precautions as would protect those with whom she came in contact, from infection." She was released from quarantine and returned to the mainland.

In 1915, Mallon started another major outbreak, this time at Sloane Hospital for Women in New York City. 25 people were infected and two died. She again left, but the police were able to find and arrest her when she brought food to a friend on Long Island. After arresting her, public health authorities returned her to quarantine on North Brother Island on March 27, 1915. She was still unwilling to have her gallbladder removed. Mallon remained confined for the remainder of her life. She became a minor Celebrity and was occasionally interviewed by the media. They were told not to accept even water from her. Later, she was allowed to work as a technician in the island's laboratory, washing bottles.

Mallon spent the rest of her life in quarantine at the Riverside Hospital. Six years before her death, she was paralyzed by a stroke. On November 11, 1938, she died of pneumonia at age 69. An autopsy found evidence of live typhoid bacteria in her gallbladder. Mallon's body was cremated, and her ashes were buried at Saint Raymond's Cemetery in the Bronx.

In August 2013, researchers at the Stanford University School of Medicine announced they were making breakthroughs in understanding the exact science behind asymptomatic carriers such as Mallon. The bacteria that cause typhoid may hide in macrophages, a type of immune cell.