Under the Byzantines a new borough began to grow on Comiso's present site around the monasteries of St. Nicolò and Saint Blaise, expanding further under the later Norman and Aragonese domination of Sicily.

Women from Italy, Europe, and other parts of the world created a peace camp in Comiso in 1983 to protest the building of the base.

[3] The missiles were eventually dismantled after the Intermediate-Range Nuclear Forces Treaty (INF) was signed by the former Soviet Union and the United States on 8 December 1987.

The main productive sectors are agriculture (wine and vegetables) and trades, including smithery, cabinet making and marble work.

Comiso is connected to the nearby towns and cities by bus service and has a railway station, which lies on the Syracuse–Ragusa–Gela–Licata–Canicattì line.