Isperih was called Kemallar during the Ottoman rule of Bulgaria and was later renamed in honour of Bulgarian khan Asparuh, whose name in Slavic was Isperih.
The town has a mixed population of Bulgarians and Turks, with an Orthodox church and a mosque being present. Isperih emerged in 1545 at the place of a medieval settlement, with the earliest known traces of human presence in the area dating from the Bronze Age. The village was first mentioned as Kemallar in an Ottoman tax register from 1573 and was renamed Isperih in 1934, becoming a town on 31 January 1960.