In 1825, Talbot joined a weaving firm established by his older brother Charles in Williamsburg, Massachusetts, where he was first employed as a carder and finisher, and quickly rose to become superintendent. His brother moved to Lowell in 1838, selling the Williamsburg mill, and began processing dyewoods in rented space at a local mill, while Thomas remained in western Massachusetts, working in area mills and continuing his education at an academy in Cummington. In 1840, the two brothers established C.P. Talbot & Co., a business partnership that lasted until Charles died in 1884. The business started out processing dyewoods for use in the textile industry, but expanded into other industrial chemical processing in 1849. The brothers acquired the Concord River water rights of the defunct Middlesex Canal Corporation in 1851, and in 1857 they established Talbot Mills in North Billerica, Massachusetts, in partnership with the Belvidere Mill Company. The business was successful, and the brothers acquired full control of that business in 1862. Thomas focused on the textile business while Charles continued to manage the dye and chemical interests, expanding the facilities in 1870 and again in 1880.