Da Vinci's most famous work of art is the Mona Lisa. Art historians believe that the Mona Lisa was painted beginning in Florence in 1503. Though there is some dispute about the subject of the painting, the prevailing theory is that it was commissioned by an Italian cloth merchant who wanted a portrait of his wife. Despite the painting's Italian origins, it was taken to Paris following da Vinci's death in 1519.

The portrait appears to be simple at first glance, but it is famous in part because of its precise mathematical proportions and attention to physical details. For example, da Vinci makes use of the golden ratio, a mathematical formula believed to influence human perceptions of beauty, to create the portions of the subject's face. He also the the finer details of the painting with great precision, creating realistic representations of the subject's skin, clothing, hair, and landscape.

The Mona Lisa arguably popularized this style of painting, which remained prevalent throughout the Renaissance. However, the painting rose to the level of fame it enjoys today when it was stolen from the Louvre museum in Paris in 1911. The theft greatly increased public interest in the painting, which was recovered two years later. Today it remains at the Louvre, where millions of people visit each year. Other famous works of art by da Vinci include The Last Supper, The Vitruvian Man, and Portrait of a Man in Red Chalk.