Mopsuestia is an ancient city of Cilicia. The founding of this city is attributed to the soothsayer, Mopsus, who lived before the Trojan war, although it is scarcely mentioned before the Christian era. Pliny the Elder calls it the free city of Mopsos (Hist. nat., V, 22), but the ordinary name is Mopsuestia or better Mompsuestia, as found in all the Christian geographers and chroniclers. At one time the city took the name of Seleucia, but gave it up at the time of the Roman conquest; under Hadrian it was called Hadriana, under Decius Decia, etc., as we know from the inscriptions and the coins of the city. Constantius II built there a magnificent bridge over the Pyramus (Malalas, "Chronographia", XIII; P.G., XCVII, 488) afterwards restored by Justinian (Procopius, "De Edificiis", V. 5) and still to be seen in a very bad state of preservation.

Christianity seems to have been introduced very early into Mopsuestia and during the third century there is mention of a bishop, Theodorus, the adversary of Paul of Samosata. The city was taken by the Arabs at the very beginning of Islam; in 686 all the surrounding forts were occupied by them and in 700 they fortified the city itself (Theophanes, "Chronogr.", A. M. 6178, 6193). Nevertheless because of its position on the frontier, the city fell naturally from time to time into the hands of the Byzantines, about 772 its inhabitants killed a great member of Arabs (op. cit., A. M. 6264). Being besieged in vain by the Byzantine troops of John Tzimisces in 964, Mopsuestia was taken the following year after a long and difficult siege by Nicephorus Phocas.

The city then numbered 200,000 inhabitants, some of whom were killed, some transported elsewhere and replaced by a Christian population. Its river, the Pyramus, formed a great harbour extending twelve miles to the sea. In 1097 the Crusaders took possession of the city and engaged in a fratricidal war under its walls; it remained in the possession of Tancred who annexed it to the Principality of Antioch. It suffered much from Crusaders, Armenians, and Greeks who lost it and recaptured it alternately notably in 1106, in 1152, and in 1171. The Greeks finally abandoned it to the Armenians. Set on fire in 1266, Mamissa, as it was called in the Middle Ages, became two years afterwards the capital of the Kingdom of Lesser Armenia, at the time that a council was held there. Although it was by this time in a state of decline it still possessed at least four Armenian churches. In 1322, the Armenians suffered a great defeat under its walls, in 1432 the Frenchman, Bertrandon , found the city occupied by the Moslems and largely destroyed. Since then it has steadily declined and today, under the name of Missis, is a little village.