Between 1780 and 1782, Barton studied at York Academy in Lancaster, Pennsylvania, where he showed an aptitude for drawing and an interest in collecting natural history specimens.

In 1786, Barton transferred to the University of Edinburgh, where he studied for two years before leaving without a degree because of financial difficulties and disagreements with two professors.

Embarrassed by his lack of credentials, Barton purchased a degree of Doctor of Medicine from the Christian-Albrechts University at Kiel in August 1796.

[6] In 1813, Barton succeeded to the professorship of the Theory and Practice of Medicine after the death of Rush but continued to lecture in natural history and botany.

Barton corresponded with naturalists throughout the United States and Europe, and he made significant contributions to the scientific literature of his day.

While he was not the first to make such a claim, he may have been the first to suggest a significant age to the mounds, as he posited that they were older than James Ussher's Biblical chronology.

Lacking evidence, Barton still speculated that Native Americans originated in Asia, anticipating the much later scientific consensus in favor of the idea.

His son Thomas Pennant Barton (born in Philadelphia in 1803; died there April 5, 1869) gathered together a notable Shakespearean library.

It comprised 2,000 of the rarest editions of Shakespeare's works, and formed, with about 10,000 miscellaneous books, one of the most important private collections in America.

His widow carried out his wishes, and the collection was acquired by the Boston Public Library, which set apart a special room for its accommodation.