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Southam was a Royal manor until AD 998, when Ethelred the Unready granted it to Earl Leofwine. When Coventry Priory was founded in 1043, Leofwine's son Leofric, Earl of Mercia granted Southam to it. The Domesday Book records the manor as "Sucham". The Priory, which in the 12th century became the first Coventry Cathedral, kept Southam until the 16th century when it surrendered all its estates to the Crown in the Dissolution of the Monasteries. The current Manor House is Grade II * listed and dates from the early 17th century.

The present parish church of St James was built in the 14th century. In the 15th century the spire was added and the chancel was rebuilt. The nave's clerestory and present roof were added in the 16th century, along with the present west door. St James' is a Grade I listed building.

In the medieval era the town minted its own local currency[citation needed] because local people found regular English currency too high in value for everyday use. In the English Civil War Charles I used Southam's mint to make new coins to pay his troops. The building is early 16th century and is now the Old Mint public house.

Southam's Holy Well, in the picturesque Stowe river valley, is a Grade II listed building and scheduled Ancient Monument, and was first recorded in the year 998. The Well was used in medieval times by local monks and for hundreds of years as the town's principal water supply. Water from a natural mineral spring feeds the semi-circular Well and pours through the mouths of carved stone gargoyles into the river. The water from the Well was said to cure eye complaints. The Holy Well and paths were renovated in 2007 using a National Lottery grant including wheelchair access and oak seats designed by artist Will Glanfield as part of his Southam Stories project, and fall within the unspoilt Stowe valley Area of Restraint as a protected landscape of special significance and value to the town.

Charles I passed through Southam just before the outbreak of the Civil War and apparently was not made welcome by the townsfolk, who refused to ring the parish church bells. On 23 August 1642, the day after King Charles 1st formally declared war on Parliament, a skirmish was fought outside the town between Parliamentary forces led by Lord Brooke and Royalist forces commanded by the Earl of Northampton. The Battle of Southam is claimed by locals to have been the first battle of the English Civil Wars. Later that year, Charles stayed in Southam before the Battle of Edgehill on 23 October 1642. In 1645 Oliver Cromwell and 7,000 Parliamentary troops stayed in the town.