It is thought that Martini was a pupil of Duccio di Buoninsegna, the leading Sienese painter of his time. Giorgio Vasari stated Simone was a pupil of Giotto di Bondone the most famous painter from Florence with whom he went to Rome to paint at old St. Peter's Basilica. Simones brother-in-law was the artist Lippo Memmi. Very little documentation survives regarding Simone's life, and many attributions are debated by art historians.
Simone was doubtlessly apprenticed from an early age, as would have been the normal practice. Among his first documented works is the "Maestà" of 1315 in the Palazzo Pubblico in Siena. A copy of the work, executed shortly thereafter by Lippo Memmi in San Gimignano, testifies to the enduring influence Simone's prototypes would have on other artists throughout the fourteenth century. Perpetuating the Sienese tradition, Simone's style contrasted with the sobriety and monumentality of Florentine art, and is noted for its soft, stylized, decorative features, sinuosity of line, and unsurpassed courtly elegance. Simone's art owes much to French manuscript illumination and ivory carving: examples of such art were brought to Siena in the fourteenth century by means of the Via Francigena, a main pilgrimage and trade route from Northern Europe to Rome.
Simone painted many frescoes, introducing the fresco technique into the Sienese school. He also painted altarpiece panels, such as the "Virgin and Child" (1320) for the Church of Saint Catherine in Pisa.
Simone lived in Assisi for a time, where he produced one of his greatest frescoes, illustrating scenes from the life of St. Martin for the chapel of St. Martin. In 1339, at the request of Pope Benedict XII, he went to Avignon, where he executed frescoes in the papal palace and the cathedral. Among his works are "Saint John the Baptist" and "The Annunciation" (1333), considered one of the greatest achievements of the Sienese school.
Simone Martini died while in the service of the Papal court at Avignon in 1344.