The royal goldsmith George Heriot had left around twenty-five thousand Pound Scots—equivalent to several tens of millions today—on his death in 1624 to found a "hospital" (at this time the name for this kind of charitable school) to care for the "puir, faitherless bairns" (Scots: poor, fatherless children) of Edinburgh.

The construction of Heriot's Hospital (as it is first called) had been started in 1628, just outside the city walls of Edinburgh.

Scottish master mason and architect William Wallace, who had served as King's Master Mason under James VI, is almost certainly the principal designer of the main building of the school, notable for its Anglo-Flemish style, which he has helped to popularize in Scotland.

After Wallace’s death in 1631, William Aytoun continues the work.