On October 8, 1842, Mother Euphrasia nominated five Good Shepherd Sisters to go to America where they might "accomplish great things." She carefully selected her delegation, choosing women "…brave enough, courageous enough to face dangers, to overcome difficulties…" The youngest was twenty-four years old; the oldest, twenty-nine. They represented five nationalities, three different languages, symbolic of the cultural diversity of the New World.

St. Mary Euphrasia blessed them: "Silver and gold I have none, but what I have I give to you. In the name of the God Shepherd, rise and go forth."

Laden with gifts and prayers, the missionaries departed on October 10, 1842. After thirty-one days at sea, they arrived in New York November 17, 1842. Traveling by buckboard and flatboat they reached their destination, Louisville, Kentucky, December 1, 1842.

Aided by collaborators and benefactors, the first missionaries to North America opened their house on September 4, 1843; on September 15, they received into their care "Mary," young woman in need.

Sisters also came from France to Canada via Montreal. They opened a house on June 11, 1844.