Thomas Handasyd Perkins is also a major industrial investor within Massachusetts.

He owns the Granite Railway, the first commercial American railroad, which has been built to carry granite from Quincy quarries to Charlestown for construction of the Bunker Hill Monument and other city buildings in Boston.

He also holds significant holdings in the Elliot textile mills in Newton, the mills at Holyoke and Lowell, New England canals and railroads, and lead and iron mines including the Monkton Iron Company in Vermont.

In addition, Perkins is politically active in the Federalist party, having serving terms as state senator and representative from 1805–1817.

Perkins becomes a philanthropist in later years.

In 1826, he and his brother, James Perkins, contribute half the sum of thirty thousand that is needed for an addition to the Boston Athenaeum, and the old Boston Athenaeum Gallery of Art is moved to James Perkins's home.