More than 20 million cars are expected to be on the roads and more than 200 rail engineering works are taking place over Easter.
The busiest day for the great getaway will be Thursday, with drivers being warned some journeys could take 90 minutes longer than usual.
The roads to avoid
The M25 between Leatherhead and Chiswell is likely to see the worst delays on Thursday, particularly between 16:00 and 18:00 BST.
According to traffic information company Inrix, the section between junctions 9 and 21 could take up to two hours and 10 minutes to cover 39 miles. It should normally take about 40 minutes.
The M6 between Crewe and Warrington is also expected to take more than twice as long as usual.
And drivers going southbound on the M5 towards the West Country are being warned delays could be almost an hour as average speeds fall to less than 25 miles per hour.
Graham Cookson, head of research at Inrix, said: "We expect significant delays over the Easter period due to a combination of factors, including the regular post-work peak, the start of the school break, people travelling on holiday, railway engineering works and Tube closures. Our advice to drivers is to consider alternative routes or avoid peak times altogether."
Highways England said more than 300 miles worth of roadworks would be completed or lifted by 06:00 BST on Thursday.
Chief executive Jim O'Sullivan said "almost all" roadworks on motorways and major roads would be removed until 18 April.
Altogether, 35 sets of roadworks, 2% of the total, will be left in place over Easter, which Highways England said were mainly road widening or managed motorway schemes. A spokesman said it was "simply not possible" to lift these for a few days as the costs were "prohibitive".
Disruption on the railway lines due to planned engineering works is also expected to impact on traffic.
Will my train be running?
About £70m worth of work, involving 13,000 staff, will take place over the Easter weekend.
Network Rail carries out work over bank holidays, such as Easter and Christmas, as the trains are typically quieter. It says more than 95% of the network will not be affected.
- Replacement buses will run between Manchester Victoria and Salford Crescent from Good Friday to Easter Sunday
- No Southeastern trains to or from Charing Cross, Waterloo East and London Bridge on Good Friday and Saturday
- No Southeastern trains at Cannon Street, Deptford, Greenwich, Maze Hill or Westcombe Park from Good Friday to Easter Monday
- Replacement buses will run between Ingatestone, Billericay and London Liverpool Street via Newbury Park from Good Friday to Easter Sunday
- Replacement buses will run between Wickford and Southminster
- Reduced services to and from Bath Spa until 23 April
London Underground work will see the Circle line closed between Edgware Road and Hammersmith for four days as well as the Hammersmith and City line between Liverpool Street and Barking and the District line between Aldgate East and West Ham.
Services will also be affected on the Metropolitan Line and Victoria Line while Whitechapel station will be closed.
What about the airports?
The airports already had their busiest day on Friday, as schools broke up for the Easter holidays.
Britain's busiest airport, Heathrow, was expecting 868,000 passengers to travel over Easter weekend with 200,000 more families than usual over the four days.
A spokeswoman said the most popular destinations were New York, Dubai and Dublin.