Southern Rail, which runs trains between England's south coast and London, warned of severe disruption as it cancelled all of its 2,284 services after workers launched three days of industrial action.
Around 1,000 drivers are involved in the strike which will affect around 300,000 passengers, including those travelling to London's Gatwick airport.
A 48-hour walkout began at midnight Monday with a further 24-hour strike planned for Friday and another six days of action in January.
The long-running dispute centres on plans for "driver-only operated trains" which mean guards would no longer be required to open and close train doors.
Union leaders have raised concerns about safety and possible job losses, although the rail company has said staffing levels will not be affected.
Passengers on routes from Brighton and other key commuter towns in southern England have already faced months of disruption to services in a series of walkouts that began in April.
The latest strike comes after the train operator's owners, Govia Thameslink Railway, lost a legal bid to halt the action.
The shutdown is expected to cause the worst disruption on Britain's railways since a series of strikes by signal workers in 1994.
Southern Rail said it was "sincerely sorry" that trains were at a standstill.
"These strikes are wholly unjustified and we must find a way forward," a company spokesman said, adding that it had invited union bosses to talks aimed at resolving the dispute.
Mick Whelan, general secretary of the train drivers' union Aslef, said the union was prepared to negotiate but added: "It's up to the company, and the government, to be flexible and end the misery of commuters."
Britain's transport minister Chris Grayling called it a "completely futile, pointless strike".
He told BBC's Radio 4 that he did not agree with the action but: "I don't have the power to order people back to work. This is a lawful strike."
The rail walkout comes after Post Office workers also voted Monday to strike in a row over job cuts, closures and pensions.
The five days of strikes next week by members of the Communication Workers Union will hit postal services during their busiest period in the run up to Christmas.
source: GULF NEWS
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