After the Indian wars subsided he experimented in educating Native Americans, believing that they must be taught to reject tribal culture and adapt to white society. In the 1870s at Fort Marion, Florida, he introduced language, religion, art, guard duty, and craftsmanship instruction to several dozen prisoners who had been chosen from among those who had surrendered in the Indian Territory at the end of the Red River War.
On November 1, 1879, he founded the Carlisle Indian Industrial School at Carlisle, Pennsylvania, the first of many nonreservation boarding schools for Native Americans. From 1879 to 1904, still on active military duty, Pratt directed the school, believing that the only way to save Indians from extinction was to remove Indian youth to nonreservation settings and there inculcate in them what he considered civilized ways. As head of the school, Pratt stressed both academic and industrial education.
Pratt's practice of Americanization of Native Americans by forced cultural assimilation, which he effected both at Fort Marion and Carlisle, was later regarded by some as a form of cultural genocide. He believed that to claim their rightful place as American citizens, Indians needed to renounce their tribal way of life, convert to Christianity, abandon their reservations, and seek education and employment among the "best classes" of Americans. In his writings he described his belief that the government must "kill the Indian to save the man". At Fort Marion and Carlisle, he sanctioned beatings to force Native Americans to stop speaking their own respective languages. Later schools run by the Bureau of Indian Affairs in the Carlisle model were marked by kidnapping and imprisonment of children at the schools, disease, sexual abuse, and suicide. Nevertheless, Pratt's approach was forward-thinking for its time inasmuch as he regarded American Indians as being worthy of respect and help, and capable of full participation in society, whereas most of his contemporaries regarded American Indians as enemies to be fought and killed.
Pratt became an outspoken opponent of tribal segregation on reservations. He believed the system as administered and encouraged by the Bureau of Indian Affairs was hindering the education and civilization of the Indian and creating helpless wards of the state. These views led to conflicts with the Indian Bureau and the government officials who supported the reservation system. In May, 1904 Pratt denounced the Indian Bureau and the reservation system as a hindrance to the civilization and assimilation of the Indian. This controversy, coupled with earlier disputes with the government over civil service reform, led to Pratt's forced retirement as superintendent of the Carlisle School on June 30 1904. This did not, however, end Pratt's support for Indian causes. A tireless speaker and letter writer, he continued his campaign for fair and humane treatment of the American Indian.
From his home in Rochester, New York, during his retirement years, Pratt continued to lecture and argue his viewpoints, but without great success. He died on April 23 1924, at the army hospital in San Francisco and was buried in Arlington National Cemetery.