Some operators are running limited services and customers have been warned to expect delays, busy journeys on unaffected lines, as well as station closures.
Passengers are advised to check their journey with National Rail Enquiries before starting.
Drivers are on picket lines at Euston, Grove Park, Kings Cross, New Cross Gate, St Pancras and Paddington stations at various times throughout the day.
It comes after another strike on Saturday, October 1, which was postponed following the death of the Queen as a mark of respect.
Members of the Associated Society of Locomotive Engineers and Firemen (Aslef) say they are battling the government and firms over pay, job cuts and terms and conditions changes.
The union represents 96% of the train drivers in England, Scotland, and Wales.
Mick Whelan, Aslef’s general secretary, said: ‘We would much rather not be in this position.
“We don’t want to go on strike - withdrawing your labour, although a fundamental human right, is always a last resort for this trade union.
“But the train companies have been determined to force our hand.”
He added: “‘They are telling train drivers to take a real terms pay cut.
“With inflation now running at 12.3% - and set, it is said, to go higher - companies are saying drivers should be prepared to work just as hard, for just as long, but for considerably less.
“The companies with whom we are in dispute have not offered us a penny.
“Train drivers kept Britain moving – key workers and goods around the country – throughout the pandemic and we deserve to be treated better than this.”
Drivers at Avanti West Coast; Chiltern Railways; CrossCountry; East Midlands Trains; Greater Anglia; Great Western Railway; Hull Trains; LNER; London Overground; Northern Trains; Southeastern; TransPennine Express; and West Midlands Trains are involved.
Daniel Mann, from the Rail Delivery Group, said: “These strikes disrupt the travel plans of millions of passengers and undermine businesses who continue to struggle with rising costs.
“This continued action will only further damage the railway’s recovery.
“While some companies are not involved, services are likely to be busy, severely disrupted or in some cases not running. Passengers should check travel advice before setting off.”
Anyone with advance, off-peak or anytime tickets affected by the strikes on October 5 can use their ticket on the day before the booked date, or up to and including 7 October.
Passengers can also change their tickets to travel on an alternate date or get a refund if their train is cancelled or rescheduled.
The London Overground is running services between Barking Riverside and Barking only, with no service on the rest of the line all day.
A TfL spokesperson said: “This action will impact London Overground, the Elizabeth line and parts of London Underground, although most of the network will be operating as usual.
“Bus services will run as normal but may be busier as a result of the rail strike action.”
For more information on how services are affected, visit the TfL website.