Members of the RMT and TSSA unions are on strike in a dispute over pay, staffing and other issues.
There are five further stoppages planned - with action on Friday 22 December threatening Christmas travel plans.
Although Virgin is expecting to run a majority of journeys, there will be no trains from London to Edinburgh.
A replacement bus service is operating between Chester and Crewe while Arriva Trains Wales is accepting customers between Chester and North Wales.
However, trains connecting London with Liverpool and Glasgow are expected to run as normal.
Passengers are being warned to check before they travel and expect services to be busier than usual.
Phil Whittingham, managing director for Virgin Trains West Coast, said: "The RMT leadership is attempting to cause disruption when many will want to travel by train to spend time with loved ones.
"We have explored a generous 3.6% pay increase, however the unions' leaderships are insisting on 4%, double the 2% average increase seen across the UK this year.
"We know how important it is for friends and families to get together over the festive season, so whilst we're sorry for the disruption we will keep the majority of our trains running with fully-trained staff onboard and at stations.
"We remain open to talks with the RMT and TSSA, and urge them to call off these strikes which will cost their members pay for no gain."