Virgin Trains revealed that one of their engineering trains had overturned late last night at Winsford, in Cheshire, leaving the line between Liverpool and London blocked.
Once the news of the derailment broke, the operator suggested that people travelling to London should consider driving to Crewe, Stoke or Stafford and boarding a train at one of those stations.
A Virgin spokesman told The Sunday Telegraph: “Due to the derailment of an engineering train at Winsford overnight, the line between Liverpool and Crewe and Warrington and Crewe is blocked.
“Due to the high number of passengers intending to travel from Liverpool/Runcorn to London for the football at Wembley it is recommended that if possible they consider driving to Crewe, Stafford or Stoke stations and use the rail services from there.
"Coaches will also be provided to connect Liverpool and Crewe and Runcorn and Stafford.
"Virgin Trains apologises for the disruption and is doing everything it can to minimise the major disruption caused by the derailment."
The schedules of National Rail and London Midland have also been affected by the incident, the two companies announcing that there would be no trains running from Liverpool to Crewe until further notice.
Steven Knight from Virgin Trains said: "Today is an extremely busy day for us out of Liverpool and we have an army of people out this morning doing everything they possibly can.
"We are at the moment attempting to get coaches to Liverpool and Runcorn so they can provide a shuttle service to Crewe and connect with our train services to London.
"My advice to anyone intending to drive into Liverpool or Runcorn to get the train, if they are able to drive to Crewe, Stoke-on-Trent of Stafford stations then they can use the train services from there."