Originally inhabited by the Nauset tribe, Eastham was the site of the 1620 landing of a hunting party from the sailing vessel Mayflower, which had stopped in Provincetown harbor on Cape Cod Bay after a rough crossing of the Atlantic Ocean.

The original lands included what are now the towns of Truro, Wellfleet, Eastham, Orleans and a small portion of Chatham.

Eastham is the birthplace of Freeman Hatch, who in 1853 set the world record for a single-hull wooden sailing vessel from San Francisco around Cape Horn to Boston at the helm of the clipper ship Northern Light.

Gustavus Franklin Swift, born in Sagamore, MA, began his first meatpacking business in Eastham.

It later moved to Brighton, MA, Albany, NY, and eventually started the meatpacking industry in Chicago.

The town is discussed at some length in Henry David Thoreau's Cape Cod as the somewhat rugged site of one of New England's largest summer "camp-meeting" evangelistic gatherings in the mid-19th century.

The town is the site of many beaches, both on the Atlantic and on Cape Cod Bay, as well as the Nauset Light, which was moved to the town in 1923 from its former location in Chatham, and the Three Sisters Lighthouses, which have since been moved away from their now-eroded perches on the coast to a field just west of Nauset Light.

Powerboats with 50 and under horsepower motors are allowed on Great Pond after receiving an inspection and sticker from the Natural Resources Department.

[21] On the national level, Eastham is a part of Massachusetts's 9th congressional district, and is currently represented by William Keating.

The town hall, police and fire department headquarters are all located along Route 6 across from Windmill Park.

The Eastham Public Library is located just west of the park, along Samoset Road (which leads from Route 6 to First Encounter Beach).

Eastham, along with Brewster, Orleans, Provincetown, Truro and Wellfleet, make up the Nauset Regional School District.

Eastham Elementary School serves students from kindergarten through fifth grade, and is located near the CCNS Visitor Center and the Schoolhouse Museum.

Another registered historic place, Nauset Light, is located on the grounds of the Cape Cod National Seashore.

The Edward Penniman House and barn, a retired whaling captain's home, is located near Fort Hill.