All trains have been cancelled from Paddington station in central London after a signal failure, causing a "total shutdown".
The travel chaos began around 4.30pm and was expected to continue until 10pm.
Services to Heathrow were suspended, along with the trains to Berkshire, South Wales and Bristol.
Great Western Railway (GWR), which operates the majority of services from London Paddington, said every line between the capital and Slough was blocked.
Network Rail - which manages Britain's railway infrastructure - and GWR said in a joint statement: "Network Rail and GWR would like to apologise to customers as a signal failure means we are not currently able to run trains into and out of London Paddington.
"Network Rail has teams on the ground working to resolve the issue as quickly as possible, however significant delays are expected to continue."
Affected passengers were advised that they may be entitled to a refund or compensation and should visit gwr.com for more information.
The station suffered similar disruption yesterday.
Commuters stranded at the station vented their disruption on social media.
Labour MP for Plymouth Luke Pollard said: "What a shambles. We need a better railway."
"Two nights running," said Bill on Twitter. "Tonight worse. Paddington total shutdown Why after all the investment WE paid for in advance you fail so badly?"
Press Association contributed to this report
