She was born in Grenoble, France, in 1769, her father a successful businessman. She was educated by the Visitation nuns and, although her father opposed her decision, she entered the Visitation Order in 1788, in the middle of the French Revolution. She was not able to make her profession because of the disruption of the Revolution and had to return home when the Visitation sisters were expelled from their convents.
During the Revolution, she cared for the sick and poor, helped fugitive priests, visited prisons, and taught children. After the Revolution, she tried to reorganize the Visitation community but was unsuccessful, so she offered the empty convent to St. Madeleine Sophie Barat, foundress of the Society of the Sacred Heart, and entered the Sacred Heart Order herself. When the bishop of New Orleans, William Du Bourg, requested nuns for his huge Louisiana diocese, St. Rose Philippine Duchesne came to the United States, arriving in New Orleans in 1818.
She and her four nuns were sent to St. Charles, Missouri, where she immediately opened a school; then at Florissant, she built a convent, an orphanage, a parish school, a school for Indians, a boarding academy, and a novitiate for her order. In 1827, she was in St. Louis where she founded an orphanage, a convent, and a parish school. Her energy and ideas were prodigious. When she was seventy-two years old, she founded a mission school for Indian girls in Kansas and spent much of her time there nursing the sick.
Her last years were spent at St. Charles, a model and inspiration to those around her, facing all the hardships of pioneer work. She died on November 18, 1852, at the age of eighty-three and was canonized in 1988. She was truly the "missionary of the American frontier," one that her beloved Potawatomi Indians called [Quah-kah-ka-num-ad], "Woman-who-prays-always."