Motorway journeys are predicted to take up to four times longer than usual on Friday as families head off on their summer holidays.
Traffic information company Inrix said four roads are likely to have delays of more than an hour.
Motorways are expected to be congested towards Devon, Cornwall, the Kentish coast and South Wales.
Inrix has predicted up to 95 minute delays along the M25 between Reigate Hill and Heathrow Airport.
The company said the busiest period is likely to be between 11:00 and 18:30 BST.
Families collecting their children from school on the last day of term for many English pupils will mix with ordinary commuting traffic, it added.
Heathrow Airport said Friday was set to be its busiest departure day of the summer with 131,546 passengers passing through.
Separate research by the RAC predicts Saturday will be the busiest day of the weekend, with traffic peaking between 11:00 and 18:00.
The RAC predicts 36.5 million "leisure" journeys in the first fortnight of many pupils' school holidays, although Scottish children finished school at the end of June.
It said drivers would experience "customary chaos" and warned of traffic hotspots on motorways to popular destinations.
RAC traffic spokesman Rod Dennis said: "This weekend will bring unwelcome customary chaos to Britain's major roads as people flock to take advantage of the first week or two of the summer holidays on home soil.
"While not as busy as Easter, which is typically the pinnacle of leisure traffic due to it being the first break for several months, the Great British summer holiday getaway begins with an initial rush for the roads this weekend as that's when the majority of schools break up.
"Sadly, for many, the summer holiday might begin stressfully as long tailbacks are inevitable, particularly in the South West on the M5 which is the main conduit to the beaches of Devon and Cornwall."
A new stretch of dual carriageway on the A30 west of Temple should provide some relief for drivers heading to Cornwall, he said.
Predicted traffic hotspots
• M5 Almondsbury Interchange and from Bristol to Taunton
• A30 and A38 Exeter to Cornwall
• A303 Andover to Ilminster
• M4 between Cardiff and Swansea
• M25 between Gatwick and M1
• A23/M23 to Brighton
• A34 and M3 south and south west to the south coast
• A47 Swaffham to Great Yarmouth
• A11 Thetford to Norwich
• M55 between Preston and Blackpool
• A14 between the Midlands and the east coast
• A590/A591 between the M6 and the Lake District
• A66 between M6 and the coast
• M53 between Liverpool and Chester
Source: RAC Traffic Watch
There are hundreds of sets roadworks planned for motorway and major trunk roads where the delay to journeys is expected to be more than 30 minutes.
Highways England will not be lifting roadworks for the weekend. It only does so when a getaway coincides with a bank holiday, such as at Christmas or Easter.
Most planned roadworks are taking place overnight Friday into Saturday.
- The M6 at J6 (Spaghetti Junction), Birmingham, exit slip roads are closed for repair over the weekend
- The M3 westbound between junctions 2 and 3 has its hard shoulder and third lane closed as well as work on the junction 4 slip road.
- The M5 northbound entry slip at J3, near Frankley, lanes one and two will be closed overnight
- The M62 eastbound exit slip road at J20, near Castleton, will be closed overnight
Highways England chief executive Jim O'Sullivan said: "I want all drivers to arrive at their destinations safely during the summer holidays. We are urging motorists to make sure they are ready to go on their journeys by checking their fuel, tyres and oil. With a few simple checks everyone will be safer."
Figures from the organisation revealed 22 drivers a day broke down last July and August because they had run out of fuel.
The RAC's figures are based on the travel plans of 3,100 motorists, with 36.5 million leisure journeys expected between Friday 21 July and Sunday 6 August.