San Gimignano was founded as a small village in the 3rd century BC by the Etruscans. Historical records begin in the 10th century, when it adopted the name of the bishop Saint Geminianus, who had defended it from Attila's Huns.

In the Middle Ages and Renaissance era, it was a stopping point for Catholic pilgrims on their way to Rome and the Vatican, as it sits on the medieval Via Francigena. The city's development also was improved by the trade of agricultural products from the fertile neighbouring hills.

In 1199, during the period of its highest splendour, the city made itself independent from the bishops of Volterra. Divisions between Guelphs and Ghibellines troubled the inner life of the commune, which nonetheless, still managed to embellish itself with artworks and architectures.

Saint Fina, known also as Seraphina and Serafina, was a thirteenth century Italian saint born in San Gimignano during 1238. Since Saint Fina died on March 12, 1253 her feast day became March 12. Her major shrine is in San Gimignano and the house said to be her home still stands in the town.

On May 8, 1300, San Gimignano hosted Dante Alighieri in his role of ambassador of the Guelph League in Tuscany.

The city flourished until 1348, when the plague that affected all of Europe, compelled it to submit to Florence. San Gimignano became a secondary centre until the nineteenth century, when its status as a touristic and artistic resort began to be recognized.