Georges attended the Jesuit College of Godrans in Dijon from the age of ten onwards. From 1723–1726 he then studied law in Dijon, the prerequisite for continuing the family tradition in civil Service. In 1728 Georges left Dijon to study mathematics and Medicine at the University of Angers in France. At Angers in 1730 he made the acquaintance of the young English Duke of Kingston, who was on his grand tour of Europe, and traveled with him on a large and expensive entourage for a year and a half through southern France and parts of Italy. Georges-Louis Leclerc had an elder brother, Pierre Daubenton (1703–1776), who wrote numerous articles for the Encyclopédie by Diderot

In 1732 he moved to Paris, where he made the acquaintance of Voltaire and other intellectuals. He first made his mark in the field of mathematics and, in his Sur le jeu de franc-carreau, introduced differential and integral calculus into probability theory; the Problem of Buffon's needle in probability theory is named after him. In 1734 he was admitted to the French Academy of Sciences. During this period he corresponded with the Swiss Mathematician Gabriel Cramer.

His protector Maurepas had asked the Academy of Sciences to do research on wood for the construction of ships in 1733. Soon afterward, Buffon began a long-term study, performing some of the most comprehensive tests to date on the mechanical properties of wood. Included were a series of tests to compare the properties of small specimens with those of large members. After carefully testing more than a thousand small specimens without knots or other defects, Buffon concluded that it was not possible to extrapolate to the properties of full-size timbers, and he began a series of tests on full-size structural members.

In 1739 he was appointed head of the Parisian Jardin du Roi with the help of Maurepas; he held this position to the end of his life. Buffon was instrumental in transforming the Jardin du Roi into a major research center and museum. He also enlarged it, arranging the purchase of adjoining plots of land and acquiring new botanical and zoological specimens from all over the world.

Buffon's Histoire naturelle, générale et particulière (1749–1788: in 36 volumes; an additional volume based on his notes appeared in 1789) was originally intended to cover all three "kingdoms" of nature but the Histoire naturelle ended up being limited to the animal and mineral kingdoms, and the animals covered were only the birds and quadrupeds. "Written in a brilliant style, this work was read ... by every educated person in Europe". Those who assisted him in the production of this great work included Louis-Jean-Marie Daubenton, Philibert Guéneau de Montbeillard, and Gabriel-Léopold Bexon, along with numerous artists. Buffon's Histoire naturelle was translated into many different languages, making him one of the most widely read authors of the day, a rival to Montesquieu, Rousseau, and Voltaire.

In 1752 Buffon married Marie-Françoise de Saint-Belin-Malain, the daughter of an impoverished noble family from Burgundy, who was enrolled in the convent school run by his sister. Madame de Buffon’s second child, a son born in 1764, survived childhood; she herself died in 1769. When in 1772 Buffon became seriously ill and the promise that his son (then only 8) should succeed him as Director of the Jardin became clearly impracticable and was withdrawn, the King raised Buffon’s estates in Burgundy to the status of a county – and thus Buffon (and his son) became a Count. He was elected a Foreign Honorary Member of the American Academy of Arts and Sciences in 1782. Buffon died in Paris in 1788.

Thanks to his talent as a Writer, he was invited to join Paris's second great academy, the Académie française in 1753. In his Discours sur le style ("Discourse on Style"), pronounced before the Académie française, he said, "Writing well consists of thinking, feeling and expressing well, of clarity of mind, soul and taste .... The style is the man himself" ("Le style c'est l'homme même"). Unfortunately for him, Buffon's reputation as a literary Stylist also gave ammunition to his detractors: The Mathematician Jean le Rond D'Alembert, for Example, called him "the great phrase-monger".

He was buried in a chapel adjacent to the church of Sainte-Urse Montbard; during the French Revolution, his tomb was broken into and the lead that covered the coffin was ransacked to produce bullets. His heart was initially saved, as it was guarded by Suzanne Necker (wife of Jacques Necker), but was later lost. Today, only Buffon's cerebellum remains, as it is kept in the base of the statue by Pajou that Louis XVI had commissioned in his honor in 1776, located at the Museum of Natural History in Paris.

In Les époques de la nature (1778) Buffon discussed the origins of the solar system, speculating that the planets had been created by a comet's collision with the sun. He also suggested that the earth originated much earlier than 4004 BC, the date determined by Archbishop James Ussher. Basing his figures on the cooling rate of iron tested at his Laboratory the Petit Fontenet at Montbard, he calculated that the age of the earth was 75,000 years. Once again, his ideas were condemned by the Sorbonne, and once again he issued a retraction to avoid further problems.

Ernst Mayr wrote that "Truly, Buffon was the father of all thought in natural history in the second half of the 18th century".

Georges Louis Leclerc (later Comte de Buffon) was born at Montbard, in the Province of Burgundy to Benjamin Francois Leclerc, a minor local official in charge of the salt tax and Anne-Christine Marlin also from a family of civil servants. Georges was named after his mother’s uncle (his godfather) Georges Blaisot, the tax-farmer of the Duke of Savoy for all of Sicily. In 1714 Blaisot died childless, leaving a considerable fortune to his seven-year-old Godson. Benjamin Leclerc then purchased an estate containing the nearby village of Buffon and moved the family to Dijon acquiring various offices there as well as a seat in the Dijon Parlement.