In the 3rd century BC, the area was inhabited by CelticScordisci. In the 1st century BC, the fort was conquered by Romans and the settlement was known as Acumincum (acumen, point). A Flavian fort was strategically situated for monitoring the lands beyond the Tisza river, the Legion camp cohors I Britannica equitata and II Adjutrix were based in the town. Jupiter Dolichenus sculptures have been found in the town. Roman fortifications were excavated in the site of Dugorep.
Slavs settled in this area in the 6th century. Old Slavic graves dating from the 6th and 7th century have been found in Slankamen. During the Middle Ages, Slankamen was a fortified city and was first mentioned in 1072 as Castrum Zalankemen. Arsenije I Bogdanović from Srem, the second Serb archbishop (1233–1263), after Saint Sava was born in the village Dabar near Slankamen. In 1325, according to a letter by pope John XXII to the Roman Catholic archbishop of Kalocsa, a public hospital was built in the village. In the 15th century, the town was a possession of the Serbian despots Stefan Lazarević and Đurađ Branković. From 1451, it was property of Hunyadis and from 1498 of John Corvin. In the 16th century it was a residence of Radoslav Čelnik, a duke of Srem.