Wetamoo was born the daughter of the Sachem of Pocasset, Chief Corbitant. The Pocasset were located in and around present day Rhode Island, and the word "Sachem" ties them to the language of the original Lenni-Lenape; a grandfather Nation to many Nations of North America and Canada. When Chief Corbitant died, Wetamoo became the Squaw Sachem.

When Wetamoo's brother-in-law died mysteriously, she became convinced that he had been poisoned by the English. This belief led to a hatred of the whites that dominated her life. During the great war of the northeast against the Pilgrims/Puritans/English, Wetamoo joined forces with the great Wampanoag Sachem, Chief Philip. Since the whites could not understand the concept of tribal living, or the role of the chief, Philip became "King Philip" to them, and the resulting war lives in history as "King Philip's War".

Wetamoo married several times but, each time, her husband became sympathetic to the whites. When this happened, Wetamoo quickly sent them on their way. She was known for her great beauty and for diplomatic skills as well as her skills as a warrior. She was ever the fighter for her people against the unfairness of white rule. She was a powerful and regal Sachem and, at the height of her tenure, she commanded some 300 warriors.

Wetamoo and her warriors were hunted continually by the Plymouth colonists during King Philip's War, but they always were successful in evading the enemy. However, during one escape down the Fall River, Wetamoo lost her footing and drowned. The Pilgrims promptly cut off her head, and displayed it on a pike in the town of Taunton.

The most complete history of Wetamoo and her leadership as Sachem of the Pocasset can be found in the memoirs of Mary Rowlandson, a white woman captured by Wetamoo during King Philip's War.