Born in Enfield, Massachusetts, Tillson immigrated to Canada in 1822. With Hiram Capron and Joseph Van Norman, Tillson was part-owner of the Normandale Iron Foundry in Norfolk County, one of Ontario's earliest iron works. In 1824, Tillson sold his share of the business and purchased 240 ha of land along Big Otter Creek after finding large deposits of bog iron in the region. In partnership with Benjamin Van Norman, Tillson dammed the stream and built a forge and sawmill in this vicinity. To encourage settlement, Tillson surveyed the town site and constructed roads. The community that he established was originally called Dereham Forge but later renamed Tillsonburg in honour of its founder.