Educated by Jesuits in Dijon, Leclerc passed his law examinations in 1726, then opted for medical studies in Angers. It was there that he encountered Newton's Principia, which influenced his later views on biology. He left Angers for Nantes following a duel. There in 1730 he met the Duke of Kingston and his tutor, with whom Leclerc toured Europe through 1732. The tour was interrupted by the death of Leclerc's mother and remarriage of his father. Upon his inheritance, he took the name of his town, and turned his attention to science.

On January 9, 1734 Buffon became an adjunct member of the French Royal Academy of Science, having contributed papers on mathematics and mechanics to the Memoires of the Academy. The following year he published a translation of Vegetable Staticks by the English botanist Stephen Hales (1677-1761). In the nextfew years Buffon was active in physics, performing experiments in heating and cooling. Hales' work formed an intellectual bridge for Buffon, as it dealt with the application of Newtonian quantitative experimentation to plant physiology. By 1739, Buffon had switched from Mechanics to Botany in the Academy, and three months later became an associate member. Upon the sudden death of the superintendent of the King's Garden, Buffon was appointed to the vacant post.  He devoted his scientific attentions to testing the strength of different woods for general use, and to establishing the optimal time of year to cut timber. His experimental work holds up remarkably well, even after more than two centuries (Zocchi, 1988). Buffon also found sufficient time to translate Isaac Newton's The Method of Fluxions and Infinite Series into French.

His fortune, and now his scientific fame, guaranteed, Buffon undertook an ambitious project. Under the auspices of the Royal Publishers, he and Louis Daubenton, a country physician and family friend from Montbard, would undertake a 15 volume compendium of natural history, the likes of which had not been attempted since Pliny in the first century. This became his life's work,  Natural History, General and Particular, which ultimately came to span 44 volumes, and is estimated to be second only to Diderot's Encyclopedia as the most widely-read work of the French Enlightenment.

No question of nature was outside the purview of Buffon's Natural History, and his answers to them inclined strongly to proximate, material causes. For example, Buffon reasons that since (1) animals are soulless material organisms, and (2) they are capable of the purest aspects of love, such as devotion and sacrifice, therefore (3) the essence of love is physical and material. Madame de Pompadour is reputed to have hit him with her fan after reading the piece.

A man of considerable vanity, in 1752 Buffon married Marie Francoise de Saint Belin-Malain, less than half his age; the marriage would last until her death in 1769.   Their daughter lived only 17 months; their son, Georges Louis Marie (nicknamed Buffonet) was born in 1764.   Buffon's land was made a county, and he was made a count, by Louis XV in 1772. Buffon secured the finest tutors possible for his son, including his protege, a young botanist named Jean Baptiste de Lamarck.

Though suffering acutely in his advanced years from kidney stones, Buffon refused surgical treatment.  When Benjamin Franklin suffered similarly, Buffon suggested blackberry preserves as a home tested remedy (Franklin Papers, Yale University).  Nevertheless, Buffon's illness could not have been helped by the 1785 scandal involving his daughter-in-law and the Duke of Orleans.  He ultimately succumbed to a kidney stone attack on April 16, 1788, at 81 years of age.  Buffonet, however, only lived six years longer than his father, dying on the guillotine in 1794.