St. Mary's is located on the north bank of the Andreafsky River. The city of St. Mary's encompasses the Yup'ik villages of St. Mary's and Andreafsky. In 1903, Jesuit missionaries set up a mission nearby to educate and care for the children orphaned by the flu epidemic in 1900-1901. The village was relocated to higher ground in 1949. St. Mary's is a Yup'ik Eskimo community dependent on fishing and subsistence activities.
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