Traces of human life were found in several locations in the area, and date back to the Neolithic (5500 BC). For Uzice is claimed that it is a town of Celtic origin, some 20 centuries old. Traces of developed settlements from the Roman and Byzantine periods were found here.

Uzice is a modern city, one of macroregional centers of Serbia, the largest city and administrative center of the Western Serbia (Zlatibor district). Municipality of Uzice occupies territory of 667 square kilometers, with 41 villages, and 82,723 inhabitants. The city itself has 53,607 inhabitants.

Back in 1537, in the village Vrutci near Uzice, the printing of Four Gospels was completed, the first book printed in Serbia. Monk Theodosius and his brethren in the monastery Rujno left a lasting monument of Serbian literacy, eight decades after the discovery Gutenbergs movable letters, which opened a new era in the exchange of messages between people.

In medieval Serbia, during the dynasty of Nemanjics (XII-XIV century) the great families of Rastislalics, Vojinovics, and Altomanovics were known. Powerful Nikola Altomanovic was bitten by Prince Lazar with the help of the Bosnian King Tvrtko sometime around 1373. After the fall of Serbia under Turkish rule in 1459, Uzice was mentioned in Turkish land registry in 1476 as a village, but in the sixteenth century it experienced rapid development. When Turkish traveler Evliya Çelebi visited it in 1664, it had the characteristics of developed city, with about 5,000 houses, and 15,000 inhabitants. Uzice was liberated from the Turks in the First Serbian Uprising in 1805, and again in 1807, and the Turkish people left it completely in 1862, after the great fire which burned the entire Turkish part of the town.

The first regular elementary and high schools in Uzice began to work in 1839, postal office - in 1841, hospital - 1853, library – 1856 and 1866.

The wars in former Yugoslavia in the last decade, economic sanctions, the international community and NATO bombing in 1999 lead to stagnation in development, decline in industrial production, and life standard of the population.