When the students arrived at Carlisle they were forced to sleep hungry on the floor on their blankets. Pratt, his wife and the Carlisle teaching staff, immediately began their immersion until "thoroughly soaked" efforts at assimilation by removing all outward signs of Indian appearances. Confused and homesick, the Lakota children wept as their long hair was cut and fell to the ground. A collective wail rose up, creating a wrenching sounding echo around the campus.

The Carlisle school was organized in a fashion quite similar to his management of the Fort Marion prison. Boys were dressed in military uniforms and given ranks. As in his Indian prison, native officers were put in charge, rewarding those who sought Pratt's favor. Students practiced marching and drilling. They were given military style ranks. Marching was done to classes and to the dining hall for meals. Inspections went into considerable detail. They even tried to ensure that the regulation red flannel underwear, which many natives found uncomfortable, was actually worn.

Cells were built to lock up students as punishment for various offenses; such as attempts to run away, a common offense.

The destruction of native languages was one of Pratt's key objectives. Children began English lessons as soon as they arrived at Carlisle. Students were punished, sometimes severely, if caught speaking their native languages, even in private. The few parents who were able to travel long distances to the school could only speak to their children in their native tongues if permission was obtained from Pratt.

Eventually Carlisle became famous for its sports teams, especially in the area of football. This produced the professional superstar, Jim Thorpe. Native games such as lacrosse were never taught at any residential school in North America. Children who played Indian games were severely punished.

Climate change, separation anxiety and lack of immunity contributed to the death of many Carlisle students. More than 175 tombstones line the campus grounds today. Prayer cloths, strings of shell and beads and small bundles of sage and sweet grass embrace tree trunks in the cemetery. Those buried on the grounds represent only a small number of the natives who perished here. Most were sent home for burial, but some had no relatives who could make the arrangements. Several hundred died on route to their families after becoming critically ill.

Although the first students at Carlisle attended voluntarily, a few years after the school was founded, compulsory methods were used. Such harsh means were applied to the children of the followers of Geronimo, many of whom attempted to hide their children. Many of these students died and were buried at Carlisle.