A member of the Jewish family of Livorno, Amedeo was the fourth child of a depressed businessman and Eugenie Garsin. His early years were poor and marked by illness. At the age of 14 he was struck by typhoid, and two years later by tuberculosis. In 1898, his 26-year-old brother Emmanuel was sentenced to six months in prison for anarchism.

In 1906, he emigrated to Paris. At first he was influenced by Toulouse-Lautrec and his work, but he was also influenced by Paul Cézanne, cubism and Picasso's blue period. He was admired for his speed of execution. He never touched his work, but those who took photographs for him described him as being exposed to the world.

Also known as "Modi" among his acquaintances, Amedeo loved women, as evidenced by his many representations such as Young Woman with Blue Eyes. He had many affairs before Beatrice Hastings entered his life. She stayed with him for almost two years and was the model for many portraits, including "Madame de Pompadour". When drunk, he was irritable and violent, but when sober, his personality was charming and shy.

On 3 December 1917, his first vernissage took place, but the show was interrupted a few hours later due to indecency. Health problems forced him to move to Nice with his wife Jeanne Hebuterne, who gave birth to a baby girl named Giovanna at the end of 1918. In May 1919, the couple returned to Paris, rue de la Grande Chaumière. His health declined rapidly. He had not been heard from for a few days when his neighbours noticed him lying in bed with Jeanne's hands, who was almost nine months pregnant. The doctor could see his despair. He died of tubercular meningitis on 24 January 1920.

The artist communities of Montmartre and Montparnasse attended his funeral. Jeanne Hebuterne, who had been taken to her parents' home, committed suicide by throwing herself out of a fifth-floor window two days after Modigliani's death.