The Cree believed in a single, all-powerful creator called Kice Manito. Kice Manito ruled supreme over all creation, which came from his will. Kice Manito was not found in a specific place like the Judeo-Christian God; instead, he was everywhere. Lesser spirit powers or Atayohkanak served as intermediaries between humans and Kice Manito.

Atayohkanak or spirits were infinite since they possessed every living thing. There was a bear spirit, a deer spirit, a spirit for every kind of tree, plant and bird. In addition, spirits, such as wisa-hketcak, the trickster, could affect the lives of humans, sometimes for better, sometimes for worse. Humans were possessed with a strong spirit force or soul called the ahtca-k, which entered the body at birth and left it at death. During a vision, the ahtca-k could temporarily leave the body and travel with a spirit guide. After death, the ahtca-k travelled beyond the Milky Way and entered the Oskaskog-Wask or Green Grass World, where men, women, and children lived a life free of cares. Matci- or Evil-Manito was the spirit of disease as well as vicious animals and plants such as cougars, snakes, and thorn bushes. With the influence of Christianity, Matci-Manito has gradually become similar to the Christian devil.

At the approach of puberty, most boys (though not all) had to go on a Vision Quest. The boy and his father or grandfather travelled to a secluded spot where they put up a brush shelter. The boy was then left alone to fast and pray until he had a vision of one or more spirit helpers. These spirits presented him with special gifts and rituals to help him through life. Sometimes, the boy would repeat the Vision Quest to seek additional gifts or because he'd been so instructed during a previous vision. Grown men also went on Vision Quests. However they were less likely to experience visions unless they had first thoroughly purified themselves with a period of fasting and sexual abstinence. Girls did not go on Vision Quests, though they had visions and acquired their own spirit helpers during their time of menstrual seclusion. The greatest gift that could be granted in a vision was the ability to cure the sick. A person who'd received this gift became a doctor or shaman. Many shamans were women.

The Cree held Sun Dances annually as well as on special occasions. Sun Dances were profoundly religious and social occasions. Everyone prayed and called on the spirits to grant them special favours, such as the recovery of a sick child. Old friends and distant family members renewed acquaintance. People who had quarrelled became friends again. Young men practiced body piercing as a way of pleasing the Creator. Christian missionaries saw the Sun Dance as an obstacle to converting the Cree and set out to suppress it. In 1884, an amendment of the Canadian Indian Act made it a criminal offense to practice the Sun Dance. It remained illegal until 1951.

Each Cree band had at least one Askitci or Pipestem bundle. This special bundle was believed to have been given by Kice Manito to Earth Man, the first human being. Inside the bundle was the Sacred Pipestem, which was not used for smoking but as a powerful peacemaking talisman. No violence could occur in the presence of the Askitci. People engaged in a quarrel, no matter how serious, were bound to make peace when the Askitci was presented to them. The Sacred Pipe Stem was also used to make peace between hostile tribes.

The earliest Christian missionaries in the Cree country were the French Jesuits who accompanied La Vérenderye to Saskatchewan in 1731. By 1820, Protestant missionaries of various denominations were accompanying Hudson's Bay Company trading expeditions. Here they encountered many Cree and many accepted the missionaries' faith. Once the Cree had been confined to reserves, government policy worked together with Christian missionaries to "civilize" the Cree. This was accomplished through laws banning traditional ways and language as well as through the establishment of the missionary-run Residential School system.

The religion of the Cree could be described as a melding of traditional Cree religion and Christianity. Many Cree regularly attend Christian church services, however many also attend Sun Dances and summer powwows. For many of the Cree, traditional healing practices continue to play a vital role parallel to non-native style medicine.