Workers from the Rail, Maritime, and Transport Union (RMT) are to walk out across three networks around the UK on Monday.
Up to 2,000 workers will go on strike across Southern Rail, Northern Rail, and Merseyrail, in a walkout which is expected to create some of the worst transport disruption since the industry went private in the 1990s.
The dispute centres on plans for driver-only trains - which brought prolonged disruption on the Southern network throughout 2016. RMT, which represents train guards, says plans for their removal would jeopardise passenger safety and place an unfair burden on train drivers.
Although around half of all trains are likely to be cancelled on the Northern and Merseyrail networks, Southern has said it plans to operate at 90% of normal capacity and claimed it is prepared to run trains through strikes.
RMT General Secretary Mick Cash has said: "The union's position on driver-only-operation (DOO) is perfectly clear.
"We will not agree to any introduction of DOO and will fight to retain the safety critical role of the guard and to keep a guard on the train."
However it is believed that the strikes on the Northern and Merseyrail networks are pre-emptive, as neither network is expected to change the role of train guards for several years.
Northern said: "Our modernisation proposals are still in early stages so it's disappointing that RMT is taking strike action.
"As part of our proposals we are prepared to offer guarantees on jobs and pay to our people."