Brunetière was born in Toulon, Var, Provence. After school at Marseille, he studied in Paris at the Lycée Louis-le-Grand. Desiring a teaching career, he entered for examination at the École Normale Supérieure, but failed, and the outbreak of war in 1870 prevented him trying again. He turned to private tuition and literary criticism. After the publication of successful articles in the Revue Bleue, he became connected with the Revue des Deux Mondes, first as contributor, then as secretary and sub-editor, and finally, in 1893, as principal editor.
In 1886 Brunetière was appointed professor of French language and literature at the École Normale, a singular honour for one who had not passed through the academic mill; and later he presided with distinction over various conferences at the Sorbonne and elsewhere. He was decorated with the Legion of Honour in 1887, and became a member of the Académie française in 1893.
The published works of Brunetière consist largely of reprinted papers and lectures. They include six series of Etudes critiques (1880–1898) on French history and literature; Le Roman naturaliste (1883); Histoire et Littérature, three series (1884–1886); Questions de critique (1888; second series, 1890). The first volume of L'Evolution de genres dans l'histoire de la littérature, lectures in which a formal classification, founded on Darwinism, is applied to the phenomena of literature, appeared in 1890; and his later works include a series of studies (2 vols, 1894) on the evolution of French lyrical poetry during the 10th century, a history of French classic literature begun in 1904, a monograph on Honoré de Balzac (1906), and various pamphlets of a polemical nature dealing with questions of education, science and religion. Among these may be mentioned Discours académiques (1901), Discours de combat (1900, 1903), L'Action sociale du Christianisme (1904), Sur les chemins de la croyance (1905).
Before 1895 Brunetière was widely known as an a rationalist, freethinking scholar. That year, however, he published an article, "Après une visite au Vatican," in which he argued that science was incapable of providing a convincing social morality and that faith alone could achieve that result. Shortly afterwards, he converted to Roman Catholicism. As a Catholic, Brunetière was orthodox and his political sympathies were conservative. He possessed vast erudition and unflinching courage. He was never afraid to diverge from the established critical view. The most honest, if not the most impartial, of magisterial writers, he had a hatred of the unreal, and a contempt for the trivial; nobody was more merciless towards the pretentious. On the other hand, his intolerance, his sledge-hammer methods of attack and a certain dry pedantry alienated the sympathies of many who recognized his remarkable intellect.