After first studying at the University of Charleroi with the painter Léon Van den Houten, Marthe Guillain took courses in literature to become a teacher. In 1914, she went to Russia where she gave private lessons in French for a friend's children. From the beginning of the October Revolution, she returned briefly to Belgium before settling in Paris to take advanced drawing courses in Fernand Cormon's studio.
In 1917, Marthe Guillain became a nurse and was sent to the battleground of the Yser saliant where she met the Brabant painter Médard Maertens who would later become her husband. At the end of the war, the couple lived in Paris and associated with Fernand Léger, Chaïm Soutine, Suzanne Valadon, Maurice de Vlaminck and Paul Signac. Guillain was keen on all aspects of the avant-garde, and took a keen liking for Van Gogh which can be seen in her virulent colors and bold schematism. Like her husband, she adopted the ideals of Fauvism and became an active member of the Brabant Fauvist movement in Belgium. In 1935, she divorced her husband and settled in the town of Watermael-Boitsfort where she established a studio.
The gallery Georges Giroux in Brussels exhibited her works from October 26 to November 10, 1942 and from October 31 to November 13, 1943 to rave reviews from the public and critics alike.
After visiting Istanbul to teach drawing, she made a trip to the Belgian Congo in 1951. With a grant from the Belgian Government she returned in 1953 for a period of eighteen months where she lived for a while with a tribe of Pygmies. She would return to Belgium and spend her last years painting abstract works much in the manner of Kandinsky, whom she had discovered some years earlier. A number of important retrospective exhibitions were held in Belgium after her death and her work can be seen today at the Museum of Charleroi and in the Royal Collection in Brussels.