The A25 exits east from Guildford, soon crossing southwards over the North Downs at Newlands Corner, to run eastward below the southern edge of the North Downs, with the road's route alternating between the Vale of Holmesdale and the Greensand Ridge, passing through Dorking, Reigate, Redhill, Nutfield, Bletchingley, Godstone, Oxted, Westerham, Brasted, Sevenoaks and Borough Green.

The A25 has junctions with several major London to south coast roads: the A24 at Dorking; the A23 at Redhill; the A22 at Godstone; and the A21 at Sevenoaks.

A short distance east of Borough Green, at Wrotham Heath, the A25 ends at a junction with the A20, which continues eastward towards Maidstone, and then south-east to Ashford, Folkestone, and then Dover.

Before leaving Guildford, the A3 connects the A25 with the A31, which continues the westward route to Farnham, before tracking south-westward to Winchester and Bournemouth.

One of the earliest sections of the M25 motorway runs parallel and to the north of the A25: hence the London Orbital Road was numbered M25.