Radial, it carries traffic from London to the Eastbourne area of the East Sussex coast, in which town it ends.

For part of its route the A22 utilises the turnpikes opened in the 18th century: By 1820 the road ran for 34 miles (54 km) from Stones End Street, Borough, London to Wych Cross.

This section incorporates the Caterham bypass, which opened in 1939 as one of the earliest such roads in the country, including the Wapses Lodge roundabout at the northern end.

To the south of the M25, the road briefly enters West Sussex at Felbridge, just to the north of East Grinstead, and the A264 between Crawley and Tunbridge Wells merges with the A22 for a short section.

The A22 bypasses East Grinstead town centre, running along a disused railway cutting, part of a line which closed as a consequence of the Beeching Report, which cut large numbers of local rail services.