During 1861, Parliamentary approval for the construction of a railway bridge at this site was obtained by the London and North Western Railway (LNWR). The design was produced by William Baker, the company's chief engineer. During 1863, preparatory work for the bridge and its sizable approach viaducts commenced. By 1868, the Runcorn Railway Bridge had been completed and it was formally opened for traffic on 10 October. The first goods traffic crossed the bridge on 1 February 1869; it was followed by the first passenger train to traverse the structure on 1 April of that year.
Since entering service, the Runcorn Railway Bridge has received few alterations. During 1965, the pedestrian footway running alongside the railway was closed to the public, but retained for maintenance access. It continues to serve rail traffic traversing the Liverpool branch of the West Coast Main Line; both of the lines traversing the structure currently have 25 kV AC overhead lines installed for use by electric traction. During the 2010s and 2020s, the bridge was subject to an extensive in-depth maintenance programme for the purpose of enabling the structure to continue in its role for another 150 years.
During 1846, the Grand Junction Railway company obtained an Act of Parliament which authorised it to construct a bridge to cross the River Mersey at the Runcorn Gap; however, a time limit of 7 years was imposed. Shortly after the passing of the Act, the Grand Junction Railway amalgamated with several other companies to form the London and North Western Railway (LNWR). As multiple other projects of the newly-combined entity were deemed to have precedence over the envisioned Runcorn Railway Bridge, work was not carried out on the project for some time. The 7 years time limit passed by without any construction activity having taken place, and thus the original powers which had been granted for the building of a railway bridge at this site quietly lapsed.
During 1861, Parliamentary approval for a railway bridge at this site was obtained by the LNWR as part of a proposal to construct a line from Aston to the southeast of Runcorn, where it would joined with the existing line from Crewe to Warrington at Weaver Junction, located to the west of Widnes, where it met the line from Warrington to Garston at Ditton Junction. This new line was 8.5 miles (14 km) long and reduced by more than 8 miles (13 km) the distance between Liverpool Lime Street and the stations south of the River Weaver. The design of the bridge was the responsibility of William Baker, the chief engineer of the LNWR.
During 1863, preparatory work for the bridge commenced at Runcorn, leading to the first stone of the structure being laid in 1864. In addition to the bridge itself, the approach viaducts were considered to be major structures in their own right as well. By 1868, the Runcorn Railway Bridge had been completed and on 21 May, there was an introductory opening journey, during which the contractor's locomotive Cheshire drew a train of 20 wagons over the bridge. It was formally opened for traffic on 10 October. The first goods traffic crossed the bridge on 1 February 1869; it was followed by the first passenger train to traverse the structure on 1 April of that year.