Henri de Toulouse-Lautrec was the only surviving son of closely related families from the provincial aristocracy of southwestern France. His father and his uncles were talented amateur artists, and Lautrec showed a keen interest and natural ability in drawing from childhood. At age thirteen he fell while getting up from a chair and broke his left femur. The following year he broke his right leg. Although it was not properly diagnosed during his lifetime, it is likely that Lautrec suffered from a bone disease (perhaps owing to the numerous consanguineous marriages in the family), and his legs stopped growing after the accidents. During his long convalescence Lautrec filled notebooks with his drawings and watercolors. His first art teacher, René Princeteau, encouraged his efforts, and Lautrec persuaded his parents to allow him to pursue further training in Paris. In 1882 he entered the atelier of Léon Bonnat, then transferred to Fernand Cormon's studio that autumn. He studied with Cormon until 1886, where he met his lifelong friends Louis Anquetin, Emile Bernard, and Vincent van Gogh.

Lautrec's work was intimately connected to the life of Montmartre from the start of his professional career. His first illustrations were published in the Montmartrois journals Le Courrier français and Le Mirliton in 1886, the same year that the Mirliton cabaret began displaying Lautrec's paintings. His work focused on the life of the butte, featuring the dance halls, circuses, cafés-concerts, and brothels that dotted the slopes of the hillside. An outgoing and social person, Lautrec befriended a heterogeneous group of Montmartre denizens, including aristocrats, streetwalkers, artists, writers, models, and cancan dancers. His portraits of his companions - often set in his studio, in neighborhood cafés, at dance halls, or at cafés-concerts - present a cross section of the population of Montmartre.

In the later 1880s Lautrec began to exhibit widely, at venues ranging from the avant-garde Les XX in Brussels to the Exposition Universelle des Arts Incohérents, the Salon des Indépendants in Paris, and the Exposition du Petit Boulevard organized by Vincent van Gogh in 1887. Vincent's brother, Theo van Gogh, began to support Lautrec's art at the gallery Boussod and Valadon in 1888, a policy continued more actively when Lautrec's childhood friend Maurice Joyant became manager following Theo's death in 1891. Lautrec created his first lithograph - the poster La Goulue: Moulin Rouge - in December 1891 and went on to design another twenty-nine posters and hundreds of prints, drawings, and paintings in the remaining ten years of his life.

In 1899, his health failing from the effects of alcoholism and syphilis, Lautrec was institutionalized for several months at an asylum near Paris, where he produced a remarkable group of drawings of the circus, drawn from memory. Soon after his release he returned to drinking, and his artistic production dropped significantly. In 1901 he suffered a stroke and died two months before his thirty-seventh birthday at his mother's estate, the Château de Malromé.