The Indian tribe that defeated Custer and put up the greatest resistance to U.S.domination was the:

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The Sioux tribe, specifically the Lakota Sioux, were responsible for the defeat of Custer at the Battle of Little Bighorn in 1876. They were also known for their successful resistance against U.S. domination during the Great Sioux War of 1876-77, one of the most significant conflicts between Native Americans and the U.S. government. While the Apache and Comanche were also fierce opponents of the U.S. government, the Sioux are most closely associated with the defeat of Custer and their resistance to U.S. domination of the Great Plains.

The Indian Tribe That Defeated Custer and Put Up the Greatest