After spending his childhood in Quimper, Brittany, France, he enrolled in the Paris Colonial School, which he left in 1897 for an artistic career. He was one of the first friends Pablo Picasso made in Paris. They met in the summer of 1901, and it was Jacob who helped the young artist learn French. Later, on the Boulevard Voltaire, he shared a room with Picasso, who remained a lifelong friend (and was included in his artwork Three Musicians). Jacob introduced him to Guillaume Apollinaire, who in turn introduced Picasso to Georges Braque. He would become close friends with Jean Cocteau, Jean Hugo, Christopher Wood and Amedeo Modigliani, who painted his portrait in 1916. He also befriended and encouraged the artist Romanin, otherwise known as French politician and future Resistance leader Jean Moulin. Moulin's famous nom de guerre Max is presumed to be selected in honor of Jacob.
Having moved outside of Paris in May, 1936, to settle in Saint-Benoît-sur-Loire, Loiret, Max Jacob was arrested on 24 February 1944 by the Gestapo, and interned at Orléans prison, (prisoner #15872). Jewish by birth, Jacob's brother Gaston had been previously arrested in January, 1944, deported to Auschwitz concentration camp, and gassed upon arrival with his sister Myrthe-Lea; her husband also deported and murdered by the Nazis. Following his incarceration at Orléans, Max was then transferred to Drancy internment camp from where he was to be transported in the next convoy to Auschwitz in Germany. However, said to be suffering from bronchial pneumonia, Max Jacob died in the infirmary of Le Cité de la Muette, a former housing block which served as the internment camp known as Drancy on 5 March.