Since the end of the 19th century, river systems across Europe have been noticeably modified by human impacts and climate change. The aim of this study is to investigate changes on river channel morphology of the Cetina River over the last 150 years. Based on historical maps, archival aerial images, and contemporary orthophoto maps, a detailed digitalisation of the river channel, fluvial bars, and islands was carried out. The river was divided into 15 segments in which we analysed the change of the active channel width and the incidence of the bars and islands. We also analysed changes of the multi-strand channels in the source area, characteristics of the part of the valley which is today submerged under the Peruća lake, and changes of the river mouth. In the period up to the mid-20th century, a partial narrowing of the channel along with the drying of the wetland zones in the source area was recorded, probably due to reduced humidity after the end of the Little Ice Age. Also, a noted growth in the area of the fluvial bars and a progradation of the river delta can be connected to the increased sediment flux due to agricultural intensification. In the last 50 years, five hydroelectric power plants were built on the river. Their operation caused the further channel narrowing by about 50% in the third of the river length. The reduction in the area of the fluvial bars by 85%, apart from the dam construction, can be related to changes in the vegetation cover which were caused by human disturbances. The results of this study thus show the impact of human activities on the river channel degradation. Moreover, they represent a starting point for the potential river restoration plans.