According to archeological findings discovered in different regions of the prefecture, as well as writings of ancient historians (Homer, Herodotus, Thucydides, Stravon) Kilkis prefecture has been inhabited since the prehistoric era. These are the ancient regions of Migdalia, Kristonia, Vottiaias and Paionias.
As Stravon mentions (end of 1st century B.C.) Paiones had inhabited the area from the prehistoric times. In modern times and until 1913, the surrounding are of Kilkis was inhabited mainly by Bulgarians. After the liberation of Kilkis in 1913 the city was inhabited by Greek refugees mainly from Stromnitsa, Thrace, Pontos, Caucasus, Asia Minor and by the end of 1926 refugees came also from Steninachites of Ano Romilia. This, together with the local characteristics, created a mixture of nations and cultures with Greek origin but with customs from their home places. These customs were preserved and revive every year through several remarkable cultural events.
Nowadays, Kilkis prefecture has a broad agricultural and stock breeding character, with grain and cereials production, as well as the so called dynamic rural products such as tobacco, cotton etc. A flourishing part of the rural economy constitutes stock production. The prefecture has remarkable stock units and organized stock zones, as well as agrobusiness mainly in dairy products. From the 1980’s the prefecture has also a strong industrial sector, mainly after the establishment of the industrial zone in Stavrochori which nowadays houses some of the best industrial units in Greece. At the same time the old industrial zone of Nea Santa, as well as the industrial park of Polikastro are being organized.
Finally, since the end of the 1990’s and after a Communal Initiative called LEADER there is a strong activity in Agrotourism sector, mainly in the mountainous areas of the prefecture.