Marie-Marguerite Dufrost de Lajemmerais was born to a French-Canadian noble family at Varennes near Montreal — the daughter of a chevalier of the Order of St. Louis. Her father died when she was seven, leaving her mother to raise six children in poverty. In 1722, at twenty-one, she married François d'Youville — a young noble who turned out to be a brutal alcoholic, an illegal trader of brandy to indigenous communities in violation of the French royal anti-alcohol prohibitions, and a serial adulterer. The marriage produced six children (four of whom died in infancy) across eight years. François d'Youville died in 1730, leaving Marguerite a 29-year-old widow with two surviving sons, no inheritance, and his debts.
She supported her surviving sons (Charles-Madeleine and François) by petty trade and by gradually re-entering Montreal Catholic confraternal life. From 1737 — encouraged by her Sulpician spiritual director Father Louis Normant — she gathered three other Montreal laywomen into a small community dedicated to the relief of the Montreal poor. The four made private religious vows on December 31, 1737, taking informal community life in a small rented house — the seed of what became the Sisters of Charity of Montreal (Sœurs Grises, the Grey Nuns).
In 1747 the deteriorated and bankrupt Hôpital Général de Montréal (founded 1693 by the Charon Brothers and by 1747 nearly closed) was placed under her direct administration by the Bishop of Quebec. Over the next twenty-four years she reformed it into the principal French-Canadian charitable institution of the late colonial period, serving the city's poor through the Plague of 1755, the Seven Years' War siege of Montreal (1760), and the early British colonial period after the Conquest of 1763. The Grey Nuns were formally constituted as a religious order in 1755 and grew into one of the major Canadian women's religious orders. Marguerite died at the Hôpital Général on December 23, 1771, twenty months after her younger son's untimely death. Beatified 1959, canonized December 9, 1990 by John Paul II — the first formally canonized Canadian-born saint.