Calne was cradled within a loop of the River Marden. By the mid-tenth century, if not before, it was the principal settlement of a large royal estate with the status of a hundred; the witan is recorded as meeting twice at the king's hall there, late in the century. This building, which would have had a protective enclosure, may be remembered in local topography by a site later known as Castle Field, approached from the town by Castle Street, which would place it on the opposite (west) side of the Marden to the town. Even more suggestive is a street named Kingsbury which passes the south side of the church and could point to a royal enclosure adjacent to a minster church, as seems to be a pattern in some other royal centres in Wessex. Though there is no unequivocal evidence Calne had a castle, if a Norman base for control did supersede a Saxon focus for royal administration, it would have been typically Norman to place it at a distance, and on the more raised slope west of the river, in conjunction with a new marketplace positioned to serve the populace on both sides of the river, and a new residential quarter with a planned layout. This hypothesis would assume there existed a river crossing – whether ford, ferry, or bridge – by the time of the establishment of a Norman enclave.

In addition to the strategic value of a site protected on three sides by river, Calne was fairly well-placed in regard to communication with other parts of the country. Along the south side of the large estate ran the Roman road between London and Bath. Through Calne itself, by the Late Middle Ages and probably earlier, passed the London-Bristol road which, more immediately, connected Calne to Marlborough and Chippenham. Other roads out of Calne went to Devizes and to Swindon via Wootton Bassett, although we cannot be sure of their condition in the Middle Ages.

Domesday presented Calne as the head of its own hundred, and accorded it the status of a borough with at least 74 burgages, divided between two lordships: a two-thirds share belonging to the king, with 45 burgess tenants; the other third representing endowments of the parish church (whose large holdings, along with the Domesday mention, are what have prompted the suggestion it may once have been a minster); the royal estate was probably coterminous with the hundred and the minster parish. The parochial manor, based around a green south of the church, was acquired by Salisbury Cathedral in 1091 and the church, dedicated to St. Mary and with its oldest surviving fabric dating to the twelfth century, assigned to a cathedral prebendary. The larger manor, incorporating what became the High Street, was granted at farm to Fulk de Cantelou, along with the hundred, around 1199. Each had its own grain mill and may have had its own market. That of the secular manor was held in a large triangular space (part of which was later reduced, by encroachment, to the High Street) on the west side of the Marden; off its base (at south) Castle Street ran westwards. There is some evidence that the east and west sides of the High Street were laid out as burgage tenements, as too a street running westwards off the north end of the High Street. The market of the prebendal manor, on the east side of the Marden, must have been held on the church green; if this was a minster church and the royal enclosure was adjacent, then the green could have been the original marketplace of the Saxon settlement. A bridge linking the two sides was in place by the sixteenth century and probably much earlier; its name of Port Bridge might just preserve an ancient term for a market town. The crossing linked the High Street market with another part of the market which included the shambles, on the other bank of the river in the opening stretch of the street leading from river to church; this stretch was known as the Strand and offers a possible alternative location for a Saxon market, a role resumed between the 1830s and 1920s.

The market on the secular manor was held by ancient right and is not documented by surviving licences, but we hear of market stalls at Calne in the early thirteenth century, while the inquisition post mortem on William de Cantelou in 1254 confirms that lordship of Calne (which produced profits of over £23 annually) included a marketplace with its tolls and other revenues. The prebendal manor may have had a long-standing market, but the case here is less clear. A licence issued to the prebend of Calne (actually the treasurer of Salisbury cathedral) in 1303 for a Saturday market could represent the initiation of a market in his manor, a retrospective formalization of something already in existence, or have been for an additional market day. In any case it was an insurance policy occasioned by a dispute with the lord of the secular manor, William de la Zouche, who was accused in 1304 of forcefully obstructing the prebendal market. The prebend argued on the basis of his licence of 1303, rather than any 'from time immemorial' principle, while William responded with the claim that King John had granted the manor, together with a Wednesday market and fair, to his grandfather William de Cantelou – this was probably a confirmation of the ca. 1199 grant – so the grandson considered the prebendal market a new-comer damaging to his own and that he was within his rights to obstruct it. The outcome of the case is not known.

The prebend also obtained, on the same occasion in 1303, licence for a July fair at the festival of St. Mary Magdalen; this too might have been simply a written confirmation of an existing right. The right of the Cantelou lords to their own fair in the borough is confirmed by the inquisition post mortem on George de Cantelou in 1273, which estimated the annual value of the tolls from market and fair at 60s., with an additional 10s. from chepingavel and brewingavel (licence fees for market trading and brewing for commercial purposes); although this was lower than the 1254 valuation of 80s. for tolls and fees, the figures must be taken as estimations, and the enquiry points to population growth in Calne since Domesday, noting that the burgages within his lordship had been sub-divided into many parts. From what little we know of Calne's economy in the medieval period, it appears typical of many small market towns, based around sale and processing of agricultural produce, leather industries, and some cloth-making – both of the latter supported by the presence of a good supply of moving water. A guildhall in the town in the thirteenth century suggests that local traders were organized to some degree, but the borough was not self-governing during the Middle Ages, leet and hundred courts, assizes of bread and ale, and market pleas being held by manorial officials.