But what do we actually know about this unique building and its famous (and not so famous) inhabitants?
The full story unfolds in a special exhibition supported by the Heritage Lottery Fund and curated by Dr Donald Smith.
The exhibition includes the results of excavations at The Netherbow, including time capsules recording how John Knox
House was saved from demolition in the 1840s.
The latest research on John Knox House and Mary, Queen of Scots is included in this exhibition in an accessible and informative way.
John Knox and the Protestant Reformers were influenced by the European movement known as Humanism.
This movement coincided with the spread of printing and of literacy, causing an intellectual revolution across the continent.
No less revolutionary was the translation of the Bible into modern European languages.
Knox travelled widely in Europe before returning to lead the Scottish Reformation.