When the Louisiana Purchase occurred in 1803, the United States came into control of the Quapaw and their territory. When Jefferson purchased the Louisiana Territory, he planned to use the area as a place to send all of the eastern tribes. This meant that tribes already there had to be moved further west. This desire to provide a homeland for eastern tribes like the Cherokee and Choctaw, along with the fact that the Quapaw tribal population had dramatically declined due to disease, prompted the government in 1818 to obtain from the Quapaw a cession of land encompassing all of what is now southern Arkansas, Oklahoma, and part of Louisiana, a 30,000,000 acre tract. The only tract of land that remained was a small parcel situated on the south side of the Arkansas River between Little Rock and Arkansas Post, but the Quapaw lost half of this either by design or through error in the transcription of the treaty for the United States Congress. Instead of preserving the Quapaw reservation, white residents saw the remaining domain essential for development if the territory were to prosper and attain statehood. Land speculators and squatters petitioned the Government to remove the Quapaw. In September, 1823, Robert Crittenden echoed the sentiments of the people to get rid of the Quapaw once and for all. They were, he said, "a poor, indolent, miserable remnant of a nation, insignificant and inconsiderable." In 1824, acting Governor Crittenden forced the Quapaw to yield what little of their lands remained. This treaty terminated all Quapaw claims to Arkansas. The Quapaw, now numbering less than 500, were removed from their native homeland to the Red River in northwestern Louisiana and were forced to join the Caddo.
The sojourn with the Caddo was disastrous for the Quapaw. They had left their home in the winter of 1825, and their journey could be remembered as the Quapaw "Trail of Tears." They were not welcomed upon arrival at the Caddo reservation. The Caddo were not prepared to accept these Arkansas refugees, and the land they gave to the Quapaw was poor. Three times in two years the Red River flooded, destroying the Quapaw's crops. Starvation was rampant. Weak with hunger, women and children died in the fields trying to tend to what was left of the crops. Over the next six years those that survived the ordeal struggled back into Arkansas. Back on their native soil they tried to take up residence, only to be reminded that they had legally signed away their lands.