The son of a chemist, William Butterfield was born in London in 1814, one of nine children. His parents were strict non-conformists who ran a chemist's shop in the Strand. He was educated at a local school before being apprenticed to Thomas Arber, a builder in Pimlico, who later became bankrupt. He studied architecture under E. L. Blackburne (1833–1836). From 1838 to 1839, he was an assistant to Harvey Eginton, an architect in Worcester, where he became articled. He established his own architectural practice at Lincoln's Inn Fields in 1840. From 1842 Butterfield was involved with the Cambridge Camden Society, later The Ecclesiological Society and contributed designs to the Society's journal, The Ecclesiologist.
Henry-Russell Hitchcock considered Butterfield's church of All Saints, Margaret Street, London, was the building that initiated the High Victorian Gothic era. It was designed in 1850, completed externally by 1853 and consecrated in 1859. Flanked by a clergy house and school, it was intended as a "model" church by its sponsors, the Ecclesiological Society. The church was built of red-brick, a material long out of use in London, patterned with bands of black brick, the first use of polychrome brick in the city, with bands of stone on the spire. The interior was even more richly decorated, with marble and tile marquetry. Just before Butterfield designed the church, John Ruskin had published his Seven Lamps of Architecture, in which he had urged the study of Italian Gothic and the use of polychromy. Many contemporaries perceived All Saints' as Italian in character, though in fact it combines fourteenth century English details, with a German-style spire.
At Oxford, Butterfield designed Keble College, in a style radically divergent from the University's existing traditions of Gothic architecture, its walls boldly striped with various colours of brick. Intended for clerical students, it was largely built in 1868–70, on a fairly domestic scale, with a more monumental chapel of 1873-6. In his buildings of 1868–72 at Rugby School, the polychromy is even more brash.