Born in Varennes, Canada, Marie Marguerite Dufrost de Lajemmerais had to interrupt her schooling at the age of 12 to help her widowed mother. Eight years later she married Francois d'Youville; they had six children, four of whom died young. Despite the fact that her husband gambled, sold liquor illegally to Native Americans and treated her indifferently, she cared for him compassionately before his death in 1730.

Even though she was caring for two small children and running a store to help pay off her husband's debts, Marguerite still helped the poor. Once her children were grown, she and several companions rescued a Quebec hospital that was in danger of failing. She called her community the Institute of the Sisters of Charity of Montreal; the people called them the "Grey Nuns" because of the color of their habit. In time, a proverb arose among the poor people of Montreal, "Go to the Grey Nuns; they never refuse to serve." In time, five other religious communities traced their roots to the Grey Nuns.

The General Hospital in Montreal became known as the Hotel Dieu (House of God) and set a standard for medical care and Christian compassion. When the hospital was destroyed by fire in 1766, she knelt in the ashes, led the Te Deum (a hymn to God's providence in all circumstances) and began the rebuilding process. She fought the attempts of government officials to restrain her charity and established the first foundling home in North America.

Blessed John XXIII, who beatified her in 1959, called her the "Mother of Universal Charity." She was canonized in 1990.