[3][4] According to religious historian Timothy L. Hall, Stiles' tenure at Yale distinguishes him as "one of the first great American college presidents.

At Yale, he studied a liberal arts curriculum characterized by an uncertain period of transition between moribund Puritan thought and that of newer thinkers like John Locke and Isaac Newton.

During his trip, the city's Trinity Church—the largest Anglican congregation in New England—sought Stiles to serve as its minister, offering him a salary of £200 sterling.

In September of the same year, Stiles was made Librarian of the Redwood Library and Athenaeum, a position that allowed him access to books at his discretion.

[13] During his years in Newport, Stiles kept an informative diary of his life and acquaintances, which detailed—among other things—his association with Portuguese merchant Aaron Lopez.

Around the same time, he wrote a joint letter with fellow Newport minister Samuel Hopkins condemning "the great inhumanity and cruelty" of slavery in the United States.

[14] During his residence in Newport, Stiles played a major role in the establishment of Brown University (then Rhode Island College).

"[7] In 1761, Stiles, along with William Ellery Jr. and Josias Lyndon, drafted a petition to the Rhode Island General Assembly to establish a "literary institution".

On January 20, Chauncey Whittelsey, pastor of the First Church of New Haven, answered a letter from Stiles:[17] The week before last I sent you the Copy of Yale College Charter ... Should you make any Progress in the Affair of a Colledge, I should be glad to hear of it; I heartily wish you Success therein.Stiles agreed to write the Charter for the college, submitting a first draft to the General Assembly in August 1763.

A revised version of the Charter written by Stiles and Ellery was adopted by the Rhode Island General Assembly on March 3, 1764, in East Greenwich.

[18] In drafting the document, Stiles combined broad-minded public statements defining Rhode Island College as a "liberal and catholic institution" in which "shall never be admitted a religious test" with private partisanship: his draft charter packed the board of trustees and the fellows of the college with his fellow Congregationalists.

[7] Stiles struck up a close friendship with Haim Isaac Carigal of Hebron during the Rabbi's 1773 residence in Newport.

[20] Stiles' records note 28 meetings to discuss a wide variety of topics from Kabbalah to the politics of the Holy Land.

Stiles believed, as did many Christian scholars of the time, that facility with the text in its original language was advantageous for proper interpretation.

In 1761, he visited a Native American village in Niantic, Connecticut, where he recorded notes on the traditional construction methods of wigwams.

According to archaeologist Edward J. Lenik, Stiles "produced one of the most important early records of petroglyphs and American Indian life in New England.

Using equipment donated to the college by Franklin, Stiles conducted the electrical experiments in New England, continuing a practice first begun by his predecessor, President Thomas Clap.

He died prematurely at Chowan County, North Carolina, on August 22, 1784, and his two daughters by his wife Sylvia (Avery) Stiles of Vermont (and formerly of Norwich, Connecticut) had their uncle Jonathan Leavitt appointed their guardian.