Born at Beziers in Lower Languedoc, the nephew of Charles Barbeyrac, a distinguished physician of Montpellier. He moved with his family into Switzerland after the revocation of the Edict of Nantes. After spending some time at Geneva and Frankfurt am Main, he became professor of belles-lettres in the French school of Berlin. Then, in 1711, he was called to the professorship of history and civil law at Lausanne, and finally settled as professor of public law at Groningen.
His fame rests chiefly on the preface and notes to his translation of Pufendorf's treatise De Jure Naturae et Gentium. In fundamental principles he follows almost entirely Locke and Pufendorf; but he works out with great skill the theory of moral obligation, referring it to the command or will of God. He indicates the distinction, developed more fully by Thomasius and Kant, between the legal and the moral qualities of action. The principles of international law he reduces to those of the law of nature, and combats, in so doing, many of the positions taken up by Grotius. He rejects the notion that sovereignty in any way resembles property, and makes even marriage a matter of civil contract. Barbeyrac also translated Grotius's De Jure Belli et Pacis, Cumberland's De Legibus Naturae, and Pufendorf's smaller treatise De Officio Hominis et Civis.
Among his own productions are a treatise, De la morale des pères, a history of ancient treaties contained in the Supplément au grand corps diplomatique, and the curious Traité du jeu (1709), in which he defends the morality of games of chance.