Sintelliners are being warned that journeys along the borough section of the M6 this weekend are likely to take twice as long as normal.
The north and soundbound section of the motorway were identified as potential traffic hotspots by information supplier Inrix.
Routes back from the coast, ports and holiday destinations dominate the list of most congested roads.
Motorists returning from Devon and Cornwall, the Lake District and East Anglia will be particularly affected, according to Inrix.
Drivers planning a trip on the M5 northbound from Exeter to Bristol are being warned to prepare for a trip of two hours and five minutes on the route, which takes one hour and 15 minutes in free-flow traffic.
The most significant delays as a proportion of traffic-free conditions are expected on the M25 clockwise from London Heathrow to Potters Bar, Hertfordshire, where a 15-minute journey in free-flow traffic is expected to take more than three times longer - some 50 minutes - during the afternoons of Thursday and Saturday.
Journeys are expected to take two hours and 20 minutes on the M6 southbound from Lymm, Cheshire, to Cannock, Staffordshire, on Monday afternoon, which is 2.8 times longer than without traffic.
Inrix chief economist Dr Graham Cookson said: “All good things must come to an end. Sadly for most, the end of the summer holidays heralds a return to work, school and traffic.
“Holidaymakers hoping to make the most of the remaining few days should be aware that traffic will be worst on Monday afternoon and evening.”
He added that the fastest way home may not be the shortest distance, and urged drivers to consider alternative routes.