The RMT union called the strike to protest plans to downgrade the role of the conductor on Southern Trains, causing cancellations across the network.
Southern, which is owned by Govia Thameslink Railway, said it will run 60 per cent of services.
RMT general secretary Mick Cash said there was "rock solid" support on the first morning of the strike, which, if completed, would be the longest industrial action on the railways since 1968, according to the BBC.
With the advent of automatic doors controlled by the driver, Southern says conductors are no longer essential, although it denies intending to scrap the jobs altogether.
The RMT, which is fighting a similar battle with Scottish railways operator ScotRail, says the move risks passenger safety.
"We share the anger and frustration of passengers and we cannot sit back while jobs and safety are compromised on these dangerously overcrowded trains," said Cash.
The action follows several one-day strikes which, along with staff shortages on Southern trains, have prompted passenger protests and calls for the government to strip the operator of its rail franchise.
"We want to run new and modern trains to provide more space and capacity and we want to make essential changes to how we operate, including giving our drivers responsibility for closing train doors so that on-board staff can focus on helping you during your journey," he said.
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