The road is important historically because not only did it lead to Port Meadow, but it was also used as a short cut to Binsey, Medley, and Wytham via a ford, called Walton Ford or Walton Well Ford. The Oxford Canal reached the outskirts of Oxford in 1789, when a coal wharf was opened at Heyfield Hutt, now the site of Hayfield Road to the north of Walton Well Road. The final section into central Oxford was ceremonially opened on 1 January 1790; it needed a bridge to be built over it to maintain the link to Port Meadow. The canal led to the industrialization of the area. In the 19th century, there was a basin and Walton Well hard for boats from the canal at Walton Well Road near the junction with Longworth Road. On the south side of the street for many years was the historic Eagle Ironworks, first established on this site by the Oxford Canal in 1825. The area has now been redeveloped as flats by Berkeley Homes, after an archaeological evaluation. During the archaeological excavation, a 17th-century pit and a possible 19th-century well were discovered to the rear of 25 Walton Well Road. railway north from Walton Well Road. The Cotswold Line railway next to the Oxford Canal was opened in 1851. In the 1850s, a railway station was planned at Walton Well. A railway line to Brentford in west London was proposed by the Oxford, Worcester and Wolverhampton Railway from this station, across the parish of St Giles, just north of the present Bevington Road and Norham Gardens. The plan never materialized. The houses on Walton Well Road were built between 1873 and 1897. Many were designed by the architect H. W. Moore in the 1880s, some in collaboration with William Wilkinson. No. 2 Walton Well Road, an imposing double-fronted residence, was the house of the ironmaster at the adjacent Lucy's foundry. On the south side of the street is the "Elijah terrace", a row of terraced houses built by Joseph Codgbrook Curtis. These include nine carved panels by the local sculptor Samuel Grafton, based in Cowley Road, Oxford, on aspects of the biblical story of the prophetElijah in the Old Testament. During the early 20th century, the poet and short story writer A. E. Coppard worked at the Eagle Ironworks in Walton Well Road, as recounted in his autobiography It's Me, O Lord!. Also in Walton Well Road was the Catholic Workers College from 1921 until 1955 when it moved to Boar's Hill south of Oxford and was renamed Plater College. Squatters moved into the area during the 1960s and 1970s, and have been dubbed 'Waltons'. Around 2000, The Waterways estate was built on the site of the British Motor Corporation's former Osberton Radiator Factory immediately to the north of Walton Well Road.
