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In the earliest document, dating from 1300, the locality appears under the name of Forum Siculorum (Market of the Seklars), and then in 1332, its name is Novum Forum Siculorum (The New Market of the Seklars), the Seklars being those inhabitants who did not become serves, but lived freely with the duty of defending the boundaries of the Hungarian Kingdom.


In 1599, duke Mihai Viteazul names the settlement "oppidi nostri Zekelyvásárhely". The name "market of the Seklars" was used until the 29th of April 1616, when Bethlen Gábor, prince of Transylvania, granted to the settlement the title of free royal town, changing also its official name to Marosvásárhely (Market place on the Mures river - in Hungarian -). The name "market on the Mures river" has been preserved, being translated in the mother tongue of several merchants, who had maintained trade relations in the area: Tîrgu-Mures - for the Romanians, Marosvásárhely - for the Hungarians, Neumarkt am Mieresch - for the Germans, etc.
The urbanisation process of the locality began at the end of the 15th century. By virtue of the privilege act granted by king Matei Corvin, in the year 1482, the town is given the right to hold three markets every year. This is also the century when artisan guilds developed, their privileges being recognised since 1493. In 1490 the Gothic-style Church of the Citadel is finalised. The town's reputation is mainly due to its position, capital of the Mures seat, as well as to the fact that it has provided home for The Transylvanian Diet for several times (among others to that of 1571, when the freedom of religious beliefs within the Principality was declared).
In 1595 the residents of Tîrgu-Mures provided duke Mihai Viteazul with help in the fights against the Turks. In 1601-1602, the town is rubbed and fired by the mercenaries hired by the Austrian Empire, led by general Basta. Between 1605-1652, on judge Borsos Tamas’s initiative (who became a famous chronicler of his time), the Citadel and other buildings with architectural and cultural value were erected. Beginning with the 16th century, Tîrgu-Mures excells as an important cultural and educational centre. The first school appears in 1492.
In 1754, in Tîrgu-Mures is built the so-called "Royal Board", where many young people, protagonists of the 1848 Revolution completed their studies in law. The greatest Hungarian poet, Petõfi Sándor, fallen in the social movement of 1848, spent his last days in Tîrgu-Mures.
In 1786, the first printing shop is established and in 1802 count Teleki Sámuel, chancellor of Transylvania, gathering over 40,000 books, lays the foundations of the documentary library that bears his name even today.