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In 1818, Duchesne boarded a ship, along with 4 companion nuns to sail to America. She felt called to serve the Native Americans in the US with Bishop DuBourg. After over 60 days at sea, she arrived in New Orleans and rested for 6 weeks at the convent of the Ursuline nuns.

After resting, Duchesne and her team boarded a steamboat to St. Louis. Upon arrival, per direction of Bishop DuBourg, they opened the first free school west of the Mississippi in St. Charles, MO. After a year, the decision was made to move the school from the remote location of St. Charles to Florissant, which was closer to St. Louis.