The line was operated by the L&SWR from the outset, who leased it from the owning company in 1858 for 50% of the gross profits, before purchasing it outright in 1878.

Despite the disparity, the GWR was not the obvious choice due to the relative position of Paddington station, west of the City of London.

[4] The line was electrified on the DC third rail system, initially at 660 volts, in sections: On Sunday 11 April 1858 a guard was killed by hitting his head on an overbridge while standing on top of a moving train.

"[7] On Saturday 13 August 1859 a train derailed at Feltham due to excessive speed and poor track condition.

[11] On Tuesday 27 June 1871 1 person was killed on a foot crossing adjacent to Twickenham station when they were struck by a train.

[16] On Wednesday 19 April 1922 a failure by shunting staff to apply brakes resulted in a light engine running away without its crew from Ascot to Virginia Water.

[18] On Tuesday 17 October 2000 a train struck a bus on the level crossing at Pooley Green between Staines and Egham.

[19] On Thursday 26 October 2000 the 0821 Weybridge to Staines train derailed about 100 yards east of Virginia Water station after slipping on wet leaves and passing a signal at danger.

[20] Early on Sunday 15 November 2009 the bridge carrying the line over the River Crane, London, partly collapsed leading to service suspension.

Services were restored eight days later on a temporary diversionary line with a 20 miles (32 km) per hour speed limit laid across the site of the disused Feltham Marshalling yard.

The stations between Waterloo and Staines, unless prohibited by bridges, are having platforms lengthened for 10-coach trains, which use converted Class 458 units.

[23] On 20 November 2014, Network Rail published a plan, the Wessex Route Study, for wide consultation;[24] its recommendations are to abolish the running of trains shorter than 10 coaches to Reading except in very low usage hours and to open more of the platforms at the former London Waterloo International with a suggested target date of 2019.

In March 2014, the Thames Valley Local Enterprise Partnership published a report showing the economic benefits of improvements to the Waterloo to Reading line.