Clémentine-Hélène Dufau's artistic inclinations became apparent at a young age. Condemned by illness to indulge in idleness, she decided to make drawings and make good use of her enforced time spent lying down. Her talent proved so good that she was able to take up studies in art once it was ensured that her sisters were married and she could not be a financial burden to her parents. In 1893, at the age of 24, the painter made her debut with the painting "Ricochets" at the Paris Salon, where she exhibited regularly from then on. In the painting, she depicted children playing by the water with a confident brushstroke and hinted at her later potential through a skillful blend of Impressionism and Realism. In 1898, a 4,000-franc grant enabled her to travel through Spain, Belgium, and the Netherlands, which she savored for an entire year and which led her to the formal language of Art Nouveau. Like many Art Nouveau painters, she enthusiastically designed postcards for the World's Fair held in Paris in 1900.

In the years that followed, she was one of the leading painters in the French capital. In 1905, for example, she was commissioned to decorate the Sorbonne's Salle des Autorités, which she painted with allegories from the fields of astronomy and mathematics, allegorizing zoology and geology, as well as the exciting subjects of radioactivity and magnetism. Between 1906 and 1912, she furnished the private Villa Arnaga of the poet Edmond Rostand, who became famous in 1897 with Cyrano de Bergerac, in the southern French town of Cambo-les-Bains with, among other things, large-scale portraits of personalities. Here Dufau had contact with Edmond's youngest son Maurice, whom, although not yet of age and homosexually oriented, she adored passionately after the death of her own mother had caused severe depression in her. Despite these private problems, Dufau also became more internationally known and participated, for example, in 1909 in the X. International Art Exhibition in the Royal Glass Palace in Munich and in the exhibition Art of Women, which was organized by the Vienna Secession. In 1909 she was even made a Knight of the Legion of Honor. During World War I, which was a drastic experience for many artists, Dufau created propaganda posters on behalf of the state. In 1930, she co-founded the Société des Femmes Artistes Modernes (FAM), which provided a haven for women artists of diverse backgrounds and ages.

When she died impoverished of stomach cancer in 1937 and was buried in a Paris cemetery for the poor, her work had already been forgotten. Born in 1869, she lived through a wide range of artistic movements. Starting with Impressionism and Realism, through the decorative painting style of Art Nouveau, striking illustrations in the context of World War I, to the beginning of classical modernism. Like many artists of the period between the world wars, she was denied the big breakthrough. It was not until the 1990s that her work was rediscovered and has since been duly appreciated.