She joined the Sisters of Loretto at age 17 and was sent to Calcutta where she taught at a high school. She contracted Tuberculosis and was sent to rest in Darjeeling. It was on the train to Darjeeling that she received her calling - what she called "an order" from God to leave the convent and work and live among the poor. At this point she did not know that she was to found an order of nuns, or even exactly where she was to serve. "I knew where I belonged, but I did not know how to get there," she said once, recalling the moment on the train.
Confirmation of the calling came when the Vatican granted her permission to leave the Sisters of Loretto and fulfill her calling under the Archbshop of Calcutta. She started working in the slums, teaching poor children, and treating the sick in their homes. She was joined a year later by some of her former students and together they took in men, women, and children who were dying in the gutters along the streets and cared for them.
In 1950 the Missionaries of Charity were born as a congregation of the Diocese of Calcutta and in 1952 the government granted them a house from which to continue their service among Calcutta's forgotten.