Occupation by past people can be divided into four major periods, based largely on changes in lithic (stone) tool technology. These periods are: Early Pre contact (11,000 to 7500 BP [Before Present]), Middle Pre contact (7500 to 2000 BP), Late Pre contact (2000 to 200 BP), and Post Contact or Historic (200 BP to Present).

It is believed that people moved into the area as soon as the last glacier retreated and the habitat became suitable. The earliest people, known as the paleo-indians, hunted bison and other big game. There are no confirmed sites from this time period located in the Park.

The earliest confirmed site dates back to 7500 BP. Projectiles from the Early Side-Notched, Oxbow, McKean, Pelican Lake, and Besant have been found in the Park. These projectiles are smaller and have side notches which are not found on earlier projectiles. These tools have been record at 11 different sites.

People in central Saskatchewan began using pottery approximately 1,900 years ago The earliest ceramic complex is known as Laurel, named after the people who used the pottery. They lived mainly in the southern boreal forest and did not penetrate far to the south and north. It is believed they are the first people to harvest wild rice. It is believed they hunted bison in small groups in the winter, coming together in larger groups to fish in the spring and fall. Later Native cultures that hunted and gathered occupied and utilized the area right up into the historic period.

According to oral history the Rocky or Woods Cree settled in vicinity of Prince Albert National Park during the mid 19th Century but traveled through the area much earlier. Traditionally the Cree did not live in one location, but followed seasonal pattern of movement.They fished, hunted and gathered fruit and berries throughout the summer and broke into small hunting parties in the fall and winter. Very little ecological impacts occurred during this time period.

Today, several First Nations communities live in the area surrounding Prince Albert National Park and have strong connections to the park's land.

The Hudson Bay Company maintained a fur trade post on Waskesiu Lake from 1886 to 1893. This post was constructed in response to establishment of a competitors' post nearby three years earlier.

Timber harvesting took place in what is now the park, with the Prince Albert Lumber Company being the major player. In 1913, the Sturgeon River Forest Reserve, which included what is now the southern third of Prince Albert National Park, was established. Severe fires in 1919 led to the abandonment of most logging operations in the area by 1921.

Commercial fishing occurred in many lakes that were to become part of the park. This activity peaked during the 1920s and did not officially end until 1961.