Its lower course begins from the Gubavica Falls, at 49 metres (161 ft) above sea level, near the village of Zadvarje, 20 kilometres (12 mi) from Omiš.

[3] Bounded to the east by the Dinaric Alps, which rise to an elevation of 2,000 metres (6,600 ft), and to the northwest by mountain Svilaja, the majority of the catchment drains calcareous rocks of Cretaceous age, predominantly limestone.

The Cetina Valley and the narrow passage at Klis have always functioned as a principal trade route between the Croatian coast and hinterland.

In the Early Bronze Age the Cetina culture, a geographically pervasive group with contacts throughout the Adriatic basin, became dominant.

[3] During the early medieval period, toponymic evidence suggests that the Cetina Valley and perhaps the river itself became a frontier between Slavic and Late Roman power.

During later periods the area was highly contested and passed between a number of regional and local powers before conquest by the Ottoman Empire during the early 16th century.