Lucien was born in Voiron. After losing his mother at the age of nineteen months, he contracted tuberculosis in his pelvis, from which he was bedridden for the first twelve years of his life, and limped until his death. In Grenoble, he became a student of the painter and monk François Joseph Girot, whose friend Jules Flandrin, an anarchist and atheist, was a major influence on Mainssieux.
In 1905, he joined the Académie Julian in Paris, where he was taught by Jean-Paul Laurens. There he met André Dunoyer de Segonzac, as well as Max Weber, through whom he met Picasso, Matisse, Marquet, Jacqueline Marval and Rouault. In spite of this association with the representatives of the currents of the time, Mainssieux did not belong to any of them, taking Cézanne as his only reference model.
For five years, he lived in Paris, but returned to Voiron in the summer to paint landscapes. Then in 1910 he left for Rome, where the architecture, monuments and sculptures enchanted him. Upon discovering Mount Palatine, which he saw for the first time while "the sun was slowly descending on the horizon" and "the palaces of the city and the hills were in a golden mist", he decided to paint it. In 1913, he exhibited this painting at the Salon d'Automne in Paris, where critics and the public noticed his style. He returned to Rome five times between 1911 and 1926.
After Italy, Mainssieux went to Africa, beginning with Tunisia. There he discovered the Muslim world, which fascinated him, and painted marabouts, oases and palm groves. After this first country of the Maghreb, to which he often returned, he visited Morocco four times, the first in 1929, and wrote an illustrated book, Le Maroc secret, which was never published. Between 1942 and 1954, he went four times to Tipaza, a coastal town located sixty kilometers from Algiers. A painter and traveler, Mainssieux spent the last twelve years of his life between Paris, Voiron and Tipaza, with a final trip in 1958 to Morocco, to Agadir. He died later that year in his native city.