Born in Yorkshire, England, into a family of builders, Spence studied as an architect, and settled in London, where he became a painter of landscapes, historical subjects and architectural scenes. Greatly inspired by the work of Sir Lawrence Alma-Tadema, Spence's best work consisted of Greek and Roman subjects. He produced large, dramatic canvases, including a series showing scenes from the Odyssey. He exhibited 11 works in the Royal Academy in the 1890s and was the subject of a solo exhibition at the Fine Art Society in 1910. His architectural work includes Jesmond Church, Newcastle, and the interior of All Saints Church, Ennismore Gardens, London.
He also exhibited at the Grosvenor Gallery and the New Gallery, and was responsible for the decorative painting in Manchester Cathedral.