The road is a main south–north link across Salisbury Plain, which is renowned for its rich archaeology, and passes many ancient points of interest along its way.

The road begins in Salisbury at the Castle roundabout and travels north out of the city, passing close to Old Sarum Castle, taking a predominantly straight line to Boscombe Down and then Amesbury before meeting the A303 at Countess roundabout, where it shares Countess Services with the major road.

Continuing north, the road passes near to Woodhenge and the Ministry of Defence Royal School of Artillery base at Larkhill.

The next significant places are Netheravon, and then Upavon where the road briefly separates into a one-way system around the village, running concurrently with the A342 to Devizes.

Between Amesbury and Durrington, a 0.8 miles (1.3 km) section of the A345 was realigned further east away from the Woodhenge scheduled monument in 1968,[1] crossing to a further west alignment and incorporating a new roundabout at its junction with the A3028.