The Peloponnese (or the Peloponnesus), the southern-most peninsula of Greece, was also known from the Frankish period as the Morea. The origin and etymology of the name Morea is obscure, but the most common derivation is from the name of the mulberry tree (morea), whose leaf is similar to the shape of the peninsula.

In late antiquity part of the province of Achaia, the Peloponnese retained its urban character. From the late 6th century, however, building activity in the peninsula practically stopped. It is still unclear whether this economic decline resulted from hostile invasions, primarily Slavic, or was also caused by a more general phenomenon of decline. The question of the Slavic invasion has been hotly discussed. Slavic penetration in the Peloponnese is indicated by the evidence of Slavic place names in the region. The Slavs seem not to have occupied the eastern cities, however, and they underwent rapid Hellenization, even though in the 14th century there were independent Slavic communities in the peninsula.

From the late 7th century the Peloponnese was part of the theme of Hellas, and from the early 9th century it was a theme in its own right, with its capital at Corinth, with Leo Sklero perhaps as its first strategos. The coasts of the Peloponnese were ravaged by Arab pirates in the 9th and 10th century until the Byzantine reconquest of Crete in 961. After that the peninsula prospered, with plentiful evidence of rich agricultural production, commerce, and industry in cities such as Corinth and Patras. The bishop of Corinth, originally metropolitan of Hellas and of the Peloponnese, was challenged, especially by the metropolitan of Patras. Over time the bishops of Lacedaemon, Argos, and Christianoupolis also gained metropolitan status.

Beginning in 1205 the leaders of the Fourth Crusade, notably William I of Champlitte and Geoffrey I Villehardouin captured most of the Peloponnese without serious struggle, and the land was divided into baronies, loosely under the authority of the Principality of Achaia. As a result of the Fourth Crusade, the Frankish conquest of the Peloponnese, the Byzantine lost all control over southern Greece from 1205 to 1262. After William II Villehardouin's defeat at the Battle of Pelagonia in 1259, however, and his cession of several fortresses to the Byzantines by the Treaty of Constantinople (1262), the Byzantines regained a foothold in the Peloponnese. During the ensuing century the Greeks reconquered the southern portion of the peninsula from the principality.

Soon after he ascended the throne, John VI Kantakouzenos created the Despotate of Morea as an autonomous province under imperial suzerainty. He sent his son Manuel Kantakouzenos to the Morea as its first despot in 1349 to reestablish order in a province troubled by dissident archontes. Manuel's long rule brought a measure of peace and prosperity to the region. Shortly after Manuel's death in 1380, John V Palaiologos made his son Theodore I Palaiologos despot; thereafter the despotate was an appanage ruled by a member of the Palaiologan family. By 1429 the despotate gained control of the entire Peloponnese by a combination of warfare and marriage diplomacy and eliminated the Principality of Achaia. Its final years (1429-60) were marked by conflict among the sons of Manuel II (Theodore II Palaiologos, Constantine XI Palaiologos, Thomas Palaiologos and Demetrios Palaiologos) over the rule of the despotate and devastating attacks by the Ottoman Turks, who were only temporarily thwarted by the construction of the Hexamilion Wall (1415) to defend the Isthmus of Corinth. The Ottomans first entered the peninsula in 1446, and after 1447 the despot of Morea became a tribute-paying vassal of the Ottoman sultan. The despotate briefly survived the Ottoman conquest of Constantinople; its capital of Mystras fell to the Ottomans in 1460, conquering the entire Peloponnese by 1460, except for Venetian strongholds such as Nauplia and Methone.

The economic basis of the despotate was agriculture (especially wine, olives, and raisins) and the production of salt and silk. An influx of Albanian immigrants provided the manpower for farming in the region, which was severely depopulated by constant fighting. The Albanians also served as mercenaries in the army. Trade was controlled by the Venetians, who also defended the coasts. The Despotate of Morea was the site of the final flowering of Byzantine culture, especially at Mystras, where many churches were built and decorated with frescoes. The court of the despot attracted numerous intellectuals, most notably the philosopher-reformer Gemistos Plethon.