During the presidency of Andrew Jackson, the most significant event concerning Native Americans was:
- They were forced to leave their homeland and move westward.
This was primarily through the implementation of the Indian Removal Act of 1830, which led to the forced relocation of thousands of Native Americans from their ancestral lands in the southeastern United States to designated "Indian Territory" west of the Mississippi River. This forced migration is most famously associated with the Trail of Tears, which specifically affected the Cherokee Nation and resulted in great suffering and loss of life.