During the entire 17th century the Kirk had been experiencing passionate internal conflicts between Presbyterians and Episcopalians (see, for example, the Bishops' Wars).

An attempt to establish a permanent university at Henricus for these purposes around 1618 failed after the Indian massacre of 1622 wiped out the entire settlement, which was not rebuilt.

Almost 70 years later, with encouragement from the Colony's House of Burgesses and other prominent individuals, Blair prepared a plan, believed by some historians to be modelled after the earlier one from Henricus, and returned to England in 1691 to petition the monarchy for a new college.

The Powhatan people had been largely decimated and reduced to reservations after the last major conflict in 1644, but the religious aspiration to educate them into Christianity was nevertheless retained, perhaps as a moral incentive to help gain support and approval in London.

[2] Blair's receipt of the charter was commemorated in 1772 by Thomas Pingo's design for the Botetourt Medal's reverse.

After Blair returned to Virginia, the trustees of the new college bought a parcel of 330 acres (1.3 km2) from Thomas Ballard for the new school.

The location chosen was at Middle Plantation, a high point on the Virginia Peninsula so named because it was equidistant from the James and York Rivers.

The State House at Jamestown burned for the third time in 1698, and as it had in the past, the legislature again took up temporary quarters at Middle Plantation.

As representative of the Bishop of London (of Oxford until 1675), Henry Compton, Blair held great power and responsibility in Virginia.

In response to complaints about dissolute clergy in the colonies, Compton had instructed Lieutenant Governor Herbert Jeffreys to investigate the situation, and then had suspended or removed those found problematic, as well as instituted a procedure to issue certificates attesting to a clergyman's orthodoxy and character and urged colonial governors not to hire those lacking such certificates.

Nonetheless, Blair worked to improve the moral condition of the people while he also defended them against the tyranny of the royal governors.

This project inspired Goodwin to advocate further restorations of other buildings, and seek sources of funding to do so, which led him to Colonial Williamsburg's greatest benefactor, Standard Oil fortune heir John D. Rockefeller Jr. and his family.

With Henry Hartwell and Edward Chilton, Blair wrote The Present State of Virginia and the College, which was published in 1727.

In the Wren Building of the College of William & Mary, a large portrait of Blair is displayed in the Great Hall.