The bank holiday weekend getaway is set to be hit by serious disruption to the rail network due to planned engineering work and strike action.
Improvement work is taking place on the West Coast Main Line which will affect services from a number of key locations, including Birmingham, Manchester, Liverpool and Glasgow.
Many passengers will be forced to make multiple changes, use replacement buses and suffer extended journey times.
Revellers attending Reading Festival are set to be hit by strike action from Saturday to Monday by members of the Rail, Maritime and Transport union as First Great Western passengers travelling towards the South West will face reduced services.
Planned works by Southern mean trains will be disrupted from the south coast and Surrey into London from Saturday to Monday.
On Sunday buses will replace trains between Bicester North and Banbury, significantly increasing journey times from the Midlands and Oxfordshire to London.
National Express is adding 67,000 extra seats to its coach network for travellers looking for an alternative method of transport in the face of rail disruption.
A spokesman for the operator said: "Demand for coach services has significantly increased on affected routes and bookings have increased by nearly 30% year-on-year in affected areas."
He added that some journeys, such as from Bournemouth or Poole to Heathrow Airport, would be quicker by coach than train as a result of the rail disruption.
Some 148,000 passengers are set to travel on the Eurostar over the bank holiday weekend, with 38,000 travelling on Friday alone.
Highways England said it was removing more than 400 miles of roadworks from motorways and major roads in a bid to reduce hold-ups.
Some 177 sets of roadworks will be completed or lifted in time for the late August getaway.
The section of the A27 hit by a plane in the Shoreham air disaster is currently closed and diversions could remain in place on the popular coastal road into the weekend.