Paul Sérusier was born in Paris in a comfortable environment. His father, François Sérusier, is a perfumer who runs the perfume company Houbigant. Paul attended high school Condorcet from 1875 and made brilliant studies, obtaining in 1882 a Bachelor of Philosophy and in 1883 a bachelor of mathematics. In 1885, he joined the school of painting and sculpture: the Academie Julian.

Serusier spends the summer of 1888 with his family in Pont-Aven and meets artists there, among whom Paul Gauguin, who immediately influences Serusier. Returned to Paris with a painting inspired by Gauguin, he conveys his enthusiasm to his classmates at the Académie Julian. The painting is called Le Talisman.

In the summer of 1889, Sérusier returned to Pont-Aven and, together with Pierre Bonnard, Maurice Denis, Henri-Gabriel Ibels and Paul-Elie Ranson, constituted the group of Nabis (Nabis means prophet in Hebrew). This group has spiritual concerns. He is interested in Orphism (doctrine of ancient Greece based on the myth of Orpheus) or in Theosophy (religious syncretism according to which all religions have a part of truth). The group of Nabis will be joined later by other artists like Édouard Vuillard, but it will last only about ten years. The dispersion takes place around 1900.

In the 1890s, Sérusier settled every summer in Brittany, first at Huelgoat, then in Châteauneuf-du-Faou with the Polish actress Gabriella Zapolska (1857-1921). He spends his winters in Paris where he exhibits regularly, especially at Impressionist and Symbolist exhibitions.

In 1902, he faced a deep depression. From 1908, he began teaching the theory of art at the Ranson Academie in Paris. This academy is a school, founded by the nabi painter Paul-Elie Ranson (1864-1909), which will operate until 1955. One of Paul Sérusier's pupils, Marguerite-Gabrielle Claude, becomes his wife in 1912.

From 1917, the painter lives mainly in Châteauneuf-du Faou with his wife. In 1921, he published an ABC of painting, a short theoretical treatise on drawing and painting, memory of all his aesthetic research.

Paul Sérusier continues to exhibit regularly until his death in 1927. His wife Marguerite, herself a painter, will survive until 1950 and will devote much to make known the work of her husband.