Native spirituality is dependent on all aspects of daily life. Sauk and Mesquakie tribes originally believed in the natural forces and forms derived directly from the Great Spirit.

Whether animate or inanimate, to the Sauk and Mesquakie people everything has a manitou, or guardian spirit. These spirits are respected and revered by all. If, for instance, a hunter kills a buffalo, he would give thanks to the buffalo's manitou for the gift of nourishment. Respect and devotion for manitous bring individuals closer in line with the Great Spirit, the creator of all, a transcendent, all-encompassing manitou.

The naming ceremony is a sacred Sauk and Mesquakie tradition that is practiced with the birth of every child. The child's name, determined typically by a respected elder, is meant so the Creator can identify and protect the "new human being." It is customary to offer the respected elder some thoughtful presents when asking for a name. Sometimes, it can take up to several months for the elder to come up with a name.

When the child arrives, family and friends are invited to a ceremony. All guests receive gifts, generally handmade. An integral part of the ceremony consists of placing a piece of the newborn's umbilical cord in a medicine bag, a small pouch containing personal items that remains with the child for life.

Since an infant's spirit is vulnerable, parents must protect and nourish their young; if a child is poorly treated, the guardian spirit may be inclined to leave.

Boys and girls learned the customs and beliefs of their tribe from an elder and/or their parents. They heard the stories of their ancestors, and learned how to fast and pray to the spirits and how to behave towards others. At puberty, they would follow sacred rituals that would bring them closer to the Great Spirit with the ultimate goal of finding one's personal manitou. Once these rituals were passed, the child was considered an adult of the tribe.

When a member of the Sauk or Mesquakie dies, the deceased's family returns the body home. The body remains in the presence of a loved one until it is ready to be buried. Following the burial, a house-like structure is built over the grave to harbor the spirit until it moves on to the next world. A fire is then built outside the house and loved ones prepare the deceased's favourite food. They throw the food into the fire to nourish the spirit. Following the ceremony, the guests walk away and avoid looking back at the grave as they risk getting tied to the spirit and consequently taken to the next world.

Sauk warriors placed a lot of importance on their medicine bags. A medicine bag is a pouch, obtained at birth, containing various items of significance to the wearer. Their contents vary from person to person as they are meant to reflect an individual's spiritual needs. Common elements include a piece of your umbilical chord, earth from your spiritual home, a piece of dried corn, and a piece of bone. However, a Sauk warrior never reveals all that is in his pouch.

Similar to other native-American tribes, Sauk and Mesquakie spiritual traditions have seen many changes with the arrival of the Europeans. In the late 1800s, Christianity had become part of Sauk and Mesquakie culture. In 1874, Moses, Keokuk's son and successor, and some of his followers declared their newfound belief in Christianity. Moses strongly encouraged his tribal members to consider Christianity as a spiritual alternative to their existing beliefs. It was not long before Christian holidays were introduced to the Sauk and Mesquakie. In 1887, Christmas was celebrated for the first time.

Despite the many efforts to convert the Sauk and Mesquakie people, it was not until the turn of the 20th century that Christianity became widespread. The growing number of native missionaries meant preaching could be conducted in the native language, thereby reaching more people.