Born in Lille, his family were Flemish and had long lived in the town or its suburbs. At the time of the poet's birth, his father, Jean-Baptiste Samain, and his mother, Elisa-Henriette Mouquet, conducted a business in "wines and spirits" at 75 rue de Paris. Samain's father died when he was quite young; it was necessary for him to leave school and seek a trade. He moved to Paris in around 1880, where his poetry won him a following and he began mixing with avant-garde literary society, and began publicly reciting his poems at Le Chat Noir. His poems were strongly influenced by those of Baudelaire, and began to strike a somewhat morbid and elegiac tone. He also was influenced by Verlaine; his works disclose a taste for indecisive, vague imagery. Samain helped found the Mercure de France, and also worked on the Revue des Deux Mondes.
Samain published three volumes of verse: Au Jardin de l'Infante (1893), which made him famous; Aux flancs du vase (1898) and Le Chariot d'or (1901). His poetic drama Polyphème was set to music by Jean Cras. Samain died of tuberculosis.
Camille Saint-Saëns set poems of Samain to music: "Six Mélodies sur des poésies d'Albert Samain" op.31 (1902-1906; orchestrated 1921)