His words – "If reason and charity cannot promote the cause of truth and piety, I cannot see how it should ever flourish under the withering fires of wrath and strife" – epitomize his career.

In 1769, he graduated as a salutatorian from the College of New Jersey (name later changed to Princeton University), and went on to study theology and philosophy under John Witherspoon.

[2] In his mid-twenties, he worked as a missionary in Virginia, and from 1775 to 1779, he served as the founder and rector of Hampden–Sydney College, which he referred to in his advertisement of 1 September 1775 as "an Academy in Prince Edward.

The situation during the winter semester of 1806–07 under Smith's presidency was characterized by little or no faculty-student rapport or communication, crowded conditions, and strict school rules — a combination that led to a student riot on 31 March–1 April 1807.

Smith was an urbane and cultivated man who sought, in the tradition of Witherspoon, to maintain orthodoxy while opposing tendencies toward rigidity and obscurantism.

The second edition of his Essay on the Causes of Variety of Complexion and Figure in the Human Species (1810) became important as a powerful argument against the increasing racism of 19th-century ethnology.

[7] He opposed the racial classifications of naturalists such as Johann Friedrich Blumenbach, Georges-Louis Leclerc, Comte de Buffon, and Carl Linnaeus.