In the Tikves region near Kavadarci, many artefacts and structures have been discovered dating back to prehistoric times.
As a settlement Kavadarci is mentioned for the first time in a document from 1823, being a small settlement within the Bitola vyllaet as the (Ottomans divided Macedonia on Skopje, Bitola and Salonica region). Kavadarci begun to form as a larger settlement, at the beginning of the 19th century.
At the period, Kavadarci used to have small number of population, around 2,000 inhabitants.
After the forming of the TMORO committee by Dame Gruev in 1894 and the Ilinden Uprising many revolutionary troops operated in the Tikves area, working with the aim of liberating Macedonia from the Ottoman Empire.
After Macedonia was divided, Kavadarci was given to the Serbs. On June 19th 1913, a rebellion was raised in the region of Kavadarci, Vatasa and Negotino. Unfortunatelly, the rebellion was bloody repressed by the Serbs.
During the 2nd World war, most notable is that 12 children from Vatasa were executed by the Buglarians, by shooting one by another.