For nearly three centuries this region has been a cradle of different civilizations and cultures. Here has been the meeting place of Thracians, Greeks and Romans; Slavs and Proto-Bulgarians; Byzantines and Latins. In the Middle Ages present day Kardzhali has been an important Christian center. Even today one can see traces of the glorious past of the First and Second Bulgarian Kingdom. It is believed that the first inhabitants of these lands were the Thracians. In the VI century, along the middle course of Arda Rive, Slavs and Proto-Bulgarians settled in. Although they established their own traditions, language and customs, they borrowed from the culture of the local population. When the Slavonic state had been formed, this region still remained within the Byzantine Empire. Only at the reign of King Simeon, it became a part of the Bulgarian state. As a prototype of Kardzhali is considered the existed area in the XI-XIV century, on the territory of the present town, which has features similar to the material culture of the old Bulgarian towns of Pliska, Preslav, Tarnovo, Messemvria. Due to its important strategic and economic importance, the lands in the Eastern Rhodopes have been continuously subjected to hostile attacks.
In 1370 - 1371 the native people lead unsuccessful battles in order to hold back the incursions of the Ottoman armies of Murad I. The Bulgarian fortresses in the region were crushed, and the majority of the population was killed, enslaved, assimilated. Another part was protected in the unaccessible forests of the Rhodope Mountain to become the guardian of the Bulgarian kin and language. The 1878 Treaty of San Stefano includes Kardzhali in Bulgaria"s borders. That same year the Berlin Treaty puts the town within the autonomous province of Eastern Rumelia. In 1886, with the Tophane Agreement, the town is returned under the direct rule of the Ottoman Sultan as a compensation for the Unification between the Principality of Bulgaria and Eastern Rumelia. During the Balkan War, on October 21 (October 8th old style calendar) 1912, Kardzhali is conquered by Haskovo Detachment and after the war remained in Bulgaria. The Battle of Kardzhali is a battle in the autumn of 1912, during the Balkan war, in which the Bulgarians (Haskovo Detachment led by Colonel Vasil Delov) defeated the Ottomans (the corps of Yaver Pasha) and permanently joined Kardzhali with the Eastern Rhodopes to Bulgaria. The anniversary of this event is celebrated annually on October 21 as a town holiday. The Liberators Monument was built in the center of the town in memory of the heroes who died for the joining of Kardzhali to Bulgaria.
In 1934 Kardzhali was declared a district center. After 1949 Kardzhali developed as a county center.
Today, Kardzhali is a regional town. It is the largest administrative, industrial, commercial and cultural center of the Eastern Rhodopes.