Prior to European colonization, the region of Lewiston was inhabited by the Androscoggin, an Abenaki people. During the 17th century, Androscoggin were among the first Native American tribes to make contact with European colonists in Maine. Relations soon deteriorated over colonial expansion, and conflicts with colonists and epidemics of infectious diseases devastated the Androscoggin, which responded by migrating to New France from 1669 onwards. By 1680, the Androscoggin had been completely driven out of Maine. The governor of New France, Louis de Buade, allocated them two seigneuries on the Saint Francis River.

A grant comprising the area of Lewiston was given to Moses Little and Jonathan Bagley, members of the Pejepscot Proprietors, on January 28, 1768, on the condition that fifty families live in the area before June 1, 1774. Bagley and Little named the new town Lewistown. Paul Hildreth was the first man to settle in Lewiston in the fall of 1770. By 1795, Lewiston was officially incorporated as a town. At least four houses that have survived from this period are currently listed on the National Register of Historic Places.

King Avenue and Ralph Avenue were named after Ralph Luthor King, who owned the land near the fairgrounds. Elliott Avenue was named after his wife, Grace O. Elliott, whose son eventually built the family home at 40 Wellman Street.