One of the oldest churches in New England, the current building was constructed around 1830 and has been ministering to the Penobscot tribe since its founding.

St. Ann's was originally a mission site established in 1668 by a French missionary named Louis-Pierre Thury. In 1702, the mission was transferred to the French Jesuits, who maintained a permanent presence until 1792, when construction of the second building was started. After the current church was built around 1830, and the site became its own parish with a full-time priest in 1926.