In early 1810, he moved to Lewiston, New York where he entered into the shipbuilding business and mercantile trade along the Great Lakes with Senior Partner, Jacob Townsend and Alvin Bronson.

His daughter Sally Ann married Henry K. Smith a future mayor of the city.

Around 1816 or 1817, Thompson moved to Black Rock, and promoted the village which was in direct competition with Buffalo for the western terminus of the Erie Canal.

In 1845, he retired from active business life and occupied himself with the management of his estate.

He died in Buffalo on March 13, 1851, and is buried in Forest Lawn Cemetery.