Kartli (Georgian: ქართლი, pronounced [ˈkʰaɾtʰli] ^ⓘ) is a historical region in central-to-eastern Georgia traversed by the river Mtkvari (Kura), on which Georgia's capital, Tbilisi, is situated. Known to the Classical authors as Hiberia, Kartli played a crucial role in the ethnic and political consolidation of the Georgians in the Middle Ages. Kartli had no strictly defined boundaries and they significantly fluctuated in the course of history. After the partition of the kingdom of Georgia in the 15th century, Kartli became a separate kingdom with its capital at Tbilisi. The historical lands of Kartli are currently divided among several administrative regions of Georgia.

The Georgians living in the historical lands of Kartli are known as Kartlelebi (ქართლელები) and comprise one of the largest geographic subgroups of the Georgian people. Most of them are Eastern Orthodox Christians adhering to the national Georgian Orthodox Church and speak a dialect which is the basis of the modern Georgian literary language.

The toponym "Kartli" first emerges in written accounts in the 5th-century Martyrdom of the Holy Queen Shushanik, the earliest surviving piece of Georgian literature. According to the medieval Georgian Chronicles, Kartli derives its name from Kartlos, the mythic Georgian ethnarch, who built a city on the Mtkvari; it was called Kartli (probably at the latter-day Armazi), a name which generalized to the country ruled by Kartlos and his progeny. Kartlos seems to be a medieval contrivance and his being the eponymous founder of Kartli is not convincing. The medieval chronicler characteristically renders this name with the Greek nominative suffix –ος (os), as Stephen H. Rapp of Georgia State University (Atlanta) assumes, "in order to impart the account with a sense of antiquity".

The term itself ultimately derives from Proto-Kartvelian root *kart- ("Georgian"), which is considered an ancient inner-Kartvelian formation by modern linguists. See ქართლი and ქართველი for more.

However, professor Giorgi Melikishvili has linked the toponym Kartli with a word karta (ქართა), found in Mingrelian (a Kartvelian language related to Georgian) and in some western Georgian dialects and meaning "a cattle pen" or "an enclosed place". The root kar occurs in numerous placenames across Georgia and, in the opinion of Melikishvili, displays semantic similarity with the Indo-European prototype; cf. Germanic gardaz ("enclosure", "garden"), Lithuanian gardas ("enclosure", "hurdle", "cattle pen"), Old Slavic gradu ("garden", also "city"), and Hittite gurtas ("fortress"). Relationships have also been sought with the Khaldi and Carduchi of the Classical sources.

The formation of Kartli and its people, the Kartveli (ქართველი) is poorly documented. The infiltration of several ancient, chiefly Anatolian, tribes into the territory of modern-day Georgia and their fusion with the autochthons played a decisive role in this process. This might have been reflected in the story of Arian-Kartli, the semi-legendary place of the aboriginal Georgian habitat found in the early medieval chronicle Conversion of Kartli.

During the 3rd century BC, Kartli and its original capital Mtskheta (succeeded by Tbilisi during the 5th century) formed a nucleus around which the ancient Georgian kingdom known to the Greco-Romans as Hiberia evolved. The role of Kartli as a core ethnic and political unit which would form a basis for the subsequent Georgian unification further increased as a result of its Christianization early in the 4th century. Located in an area influenced by both the Byzantine and Iranian civilizations, Kartli developed a Christian culture, aided by the fact that it was the only Kartvelian area with its own written language. With the consolidation of Arab rule in Tbilisi during the 8th century, the political capital of Kartli shifted to its southwest, but the Georgian literati of that time afforded to Kartli a broader meaning to denote all those lands of medieval Georgia that were alike by religion, culture, and language. In one of the most-quoted passages of medieval Georgian literature, the 9th-century writer Giorgi Merchule asserts: "And Kartli consists of that spacious land in which the liturgy and all prayers are said in the Georgian language. But [only] the Kyrie eleison is said in Greek, [the phrase] which means in Georgian "Lord, have mercy" or "Lord, be merciful to us".

After the unification of various Georgian polities into the kingdom of Georgia early during the 11th century, the names "Kartli" and "Kartveli" became a basis of the Georgian self-designation Sakartvelo. The Georgian circumfix sa-X-o is a standard geographic construction designating "the area where X dwell", where X is an ethnonym.