Nelligan attended the Collège Sainte-Marie in Montreal but abandoned his studies to concentrate on writing. In 1899, after three years of intense poetic activity, he was hospitalized for schizophrenia; he spent the rest of his life in institutions.

Like other members of the Montreal School, Nelligan was influenced by the French Parnassian and Symbolist poets; his work recalls that of Charles Baudelaire (Baudelaire, Charles) and Paul Verlaine (Verlaine, Paul) in particular. Nelligan's poems, known for their lyricism, are written in a melancholy and nostalgic, and sometimes hallucinatory, voice; they are noted for their unusual symbols, evocative language, and musical rhythms. Themes of dreaming, childhood, music, and death pervade his work. Nelligan used conventional poetic forms: of his approximately 160 poems, nearly half are sonnets or rondels. The best known are "Le Vaisseau d'or" (“The Ship of Gold”) and "La Romance du vin" (“The Song of Wine”).

Nelligan's reputation grew steadily during the 20th century. The most comprehensive critical edition of his work, Poésies complètes, appeared in 1952; an English translation of his complete works was published in 1983. Le Prix Émile Nelligan, which began in 1979, is awarded to outstanding poets.