Situated on the east bank of the River Avon between two crossing points, Amesbury is close to a Romano-British settlement and a pre-Roman hilltop fort reputed in folklore of the Middle Ages as a stronghold of Ambrosius Aurelianus; Amesbury may have taken its name from this uncertain association. In the tenth century it had sufficient importance for the witan to meet there, and it has been conjectured that Amesbury was an administrative centre for royal estates of the region, with at least a partial protective enclosure – the river offering a natural defence to north and west – which would make it an early burh. For a rural settlement, it was home to a good-sized, though scattered, population by the time of Domesday, remaining a royal vill until the 1140s, when granted to the Earl of Salisbury. An abbey had been founded there ca. 979, but it was a relatively poor one and was superseded by a well-endowed priory in 1177, a new house being built for both monks and nuns over the next few years; the priory was grand enough to attract royal visitors, while the old abbey church was converted to a parish church. One of the Avon crossings carried a route connecting London and the south-west, the part of this road passing through Amesbury, and by the old abbey site, being known as High Street in 1364. The stretch of this road closest to the large priory precinct – which consumed the north-western sector of Amesbury, with its rear towards the Avon and its main entrance facing the High Street – attracted settlement in an apparently unplanned fashion.

Amesbury was held by William Longespée, Earl of Salisbury by marriage, when licence was acquired in 1219 for a Thursday market, and in 1252 his grandson obtained grant of a fair, along with confirmation of the market. In 1317 a Saturday market was granted the priory, though only one market location is known in the town. At the same time a fair was granted the priory; this may have been, rather than a transfer of fair rights or an entirely separate event, an extension of the period of the earlier fair, with its focus shifted to trading activities within the priory precinct. The priory evidently wanted to share in the profits from the town's growing commerce. A burgess of Amesbury is referenced in 1314 and in 1364 22 burgages are mentioned as being held of the manor; shops and shambles are also heard of in that century.

The apex of a roughly triangular marketplace opened off the High Street forming quite a broad area at rear. It is around this space, and the lanes running off it, that a planned town is believed to have been laid out; it has been conjectured that two lanes leading away from the base of the triangle might have been part of the town plan, intended to facilitate traffic from south and south-east of the town reaching the market. Medieval Amesbury was the administrative centre of a hundred, but not a self-governing borough. Although its market was not of great consequence, it was one of the more prosperous towns in the county during the Middle Ages, thanks largely to the needs of the priory (which became exclusively a nunnery in the fifteenth century) and the pilgrims or other visitors it attracted. A slow decline began during the post-medieval period, spurred on by loss of the priory at the Dissolution.