From the close of the twelfth century, the principle Mellerstain lands belonged to the de Haitley family. Over the succeeding four and a half centuries, the properties changed hands numerous times among the notable Borders families, including the Haliburtons and Napiers, until, in 1642, they were made over by Royal Charter to George Baillie of Jerviswood, son of a prosperous merchant burgess of Edinburgh. He lived in a tower house on the site of the present-day mansion.

The times were not propitious for building. The Civil War was in progress when George Baillie died in 1646, and was succeeded by his eldest surviving son, Robert, who came into conflict with the authorities. In 1676 he was imprisoned and fined £500 sterling (an immense sum in those days), for rescuing his brother-in-law from what he thought to be an illegal arrest. It was while he was incarcerated in the Edinburgh Tolbooth that Sir Patrick Hume, afterwards Earl of Marchmont, wishing to communicate with him, entrusted the dangerous mission to his eldest daughter Grisell, then a child of twelve.

Robert Baillie, as a staunch Covenanter, was strongly opposed to the policy of the Government, and in 1684 he was arrested for high treason and condemned to death. His estate was forfeited, as was also that of Sir Patrick Hume. Sir Patrick and his family fled to Holland and were speedily followed by young George Baillie, penniless after his father's death. He had already met the heroic little Grisell, and in exile the friendship ripened, although he had nothing yet to offer her but the pay of a junior officer in the Prince of Orange's Horse Guards. Then, in 1688, came a dramatic change of fortune. The Prince of Orange set out on a journey which was to make him William III of England, and Sir Patrick Hume and George Baillie sailed with him. Both their estates were restored and in September 1691 Grisell Hume became Grisell Baillie.