One of the worse times in our American history, imho, was the Trail of Tears, the forcible relocation of many Native Americans. Five tribes the Cherokee, Chickasaw, Muscogee-Creek, and Seminole all living in the deep south were relocated to the Indian Territory, what is now known and most of Oklahoma and some of Kansas.
The trail was not a one time event, each tribe was relocated at different intervals. The act was called "The Indian Removal Act of 1830" Wikipedia has a good article referring to the act voted on and signed by President Andrew Jackson.
Choctaw from Alabama, Mississippi and Louisiana were marched out in 1831
1832 was the removal of the Seminole tribe from Florida.
The Creek were removed in 1834 also from Alabama & Georgia
The Chickasaw in 1837 Mississippi River area.
Cherokee in 1838 from North Carolina, Georgia because gold had been found on their lands.
The trail took the lives of many as exposure, disease and starvation hit them as they were en route. 46,000 were taken before the Cherokee, I couldn't find figures on how many Cherokee were taken but at least 4,000 died on the trail. I've found figures from 17,000 to 24,000