The Prefecture of Xanthi is located in the west of the Thrace region covering an area of 1,793 km² and is bordered by the sea to the south. The land is entirely mountainous in the north with its highest peak of Mount Koula at 1,827 m on the border with the Bulgaria. To the south is the valley of Xanthi. The region has two rivers: the large Nestos River on the border of Kavala and the small Xanthos River. In the region there are therapeutic springs near the village of Nea Kessani with good curative capacities, 20 km from the city of Xanthi.

In the Prefecture of Xanthi, Greek traditions coexist with those of Turks, who long dominated in this region in the past. Both Mosques and Christian churches can be found in its towns.

Places of interest are: the archeological site of Avdera was birthplace of Democritus and Lake Vistonis at Portolagos, a significant wetland.

The climate is milder in the south and colder in the north.