The area was once a major Abenaki Indigenous peoples of the Americas village known as Pequawket, meaning "crooked place," a reference to the large bend in the Saco River.

It was inhabited by the Sokokis tribe, whose territory along the stream extended from what is now Saco on the coast, to Conway, New Hampshire in the White Mountains.

[4] For a while the tribe was not hostile to English settlements, even hiring British carpenters to build at Pequawket a 14-foot (4.3 m) high palisade fort as protection against their traditional enemy, the Mohawks.

In 1713, Sokokis sachems signed the Treaty of Portsmouth to ensure peace with English colonists.

On the eve of American independence, the Province of Massachusetts Bay granted township privileges to Fryeburg.

Excellent soil helped Fryeburg develop into a prosperous agricultural center, and the first gristmill was established using Saco River water power in 1766.

Other mills and factories produced lumber, leather, harness, tinware, cheese and canned vegetables.

After the Civil War, the Portland and Ogdensburg Railroad passed through town, bringing tourists escaping the heat and pollution of cities.

Tourists began arriving by automobile after designation of the Theodore Roosevelt International Highway in 1919 (identified as United States Route 302 since 1935).

Before his career as a statesman, Daniel Webster taught for a year at the school, one of the oldest of its type in the nation.

Two years later, Dr. Krasker's wife Gertrude founded Forest Acres Camp For Girls.

[15] U.S. Route 302 in Fryeburg is the second largest point of entry for highway traffic into the state of Maine, next to Interstate 95 in Kittery.

It is also home to Har-Mac Steel, a manufacturer of structural reinforcing materials for the construction industry.

Their products are being used in the construction of tunnels, bridges and major buildings in locations such as Chicago, New York and Puerto Rico.