Negotino is in a vineyard region and the gates of the Tikveš plain, known for its fertility, are located nearby.

Along with Kavadarci, Negotino is known as the home of North Macedonia's best wine and rakija (brandy).

[citation needed] A settlement in the location of modern Negotino existed and developed in antiquity.

Between 278 and 242 BC, a city was founded by King Antigonus II Gonatas, under the name of Antigoneia (Αντιγονεία in Greek).

Antigoneia was situated some twelve Roman miles south of the ancient city of Stobi, on the road to Thessaloniki, at the location of modern Gradiste, near the railway station of Negotino.