The permanent nucleus of Isauria was north of the Taurus range which lies directly to south of Iconium and Lystra. Lycaonia had all the Iconian plain; but Isauria began as soon as the foothills were reached. Its two original towns, Isaura Nea and Isaura Palaea, lay, one among these foothills (Doria) and the other on the watershed (Zengibar Kalesi).
In the 4th century BC, Isauria began as it would end, and became the wild district about Isaura Palaea and the heads of the Calycadnus. When the capital, Isaura (also known as Isaura Vetus or Isaura Palaea), a strongly fortified city at the foot of Mt. Taurus, was besieged by Perdiccas, the Macedonian regent after Alexander the Great's death, the Isaurians set the place alight and let it perish in flames rather than submit to capture.
The Isaurians were brought partially under control (76–75 BC) by the Romans. During the war of the Cilician and other pirates against Rome, the Isaurians took so active a part that the proconsul P. Servilius deemed it necessary to follow them into their rugged strongholds, and compel the whole people to submission, an exploit for which he received the title of Isauricus (75 BC). The Isaurians were afterwards placed for a time under the rule of Amyntas, king of Galatia; but it is evident that they continued to retain their predatory habits and virtual independence. In the 3rd century they sheltered the rebel emperor Trebonianus Gallus.
In the early 4th century all Cilicia was detached by order of Diocletian for administrative purposes from the northern slope of Taurus, and we find a province called at first Isauria-Lycaonia, and later Isauria alone, extending up to the limits of Galatia, but not passing Taurus on the south. Pisidia, part of which had hitherto been included in one province with Isauria, was also detached, and made to include Iconium. In compensation Isauria received the eastern part of Pamphylia.
In the 4th century they were still described by Ammianus Marcellinus as the scourge of the neighbouring provinces of Asia Minor but they were said to have been effectually subdued in the reign of Justinian I.
This comparatively obscure people produced two Byzantine emperors, Zeno, whose native name was Traskalisseus Rousoumbladeotes, and Leo III, who ascended the throne of Constantinople in 718, reigned until 741, and became the founder of a dynasty of three generations. The empire used Isaurians as soldiers, generals and at one point they even formed part of the emperor's personal guard, the Excubitores.
Several sources consider Isaurians as an ethnic designation for the ancient Kurds in the Taurus region or the ancestors of the Modern Kurds. According to the Catholic Encyclopedia, Isaurians probably included tribes of Kurds in the Taurus ranges in the southeast of Asia Minor.