Meandering rivers are among the most dynamic Earth-surface systems, which generally appear in fertile valleys, the most valuable lands for agriculture and human settlement. Landsat time series and morphological parameters are complementary tools for exploring river dynamics. Karun River is the most effluent and largest meandering river in Iran, which keeps the Karun’s basin economy, agriculture, and industrial sections alive; hence, investigating morphological changes in this river is essential. The morphological characteristics of Karun have undergone considerable changes over time due to several tectonic, hydrological, hydraulic, and anthropogenic factors. This study has identified and analyzed morphological changes in Karun River using a time series of Landsat imagery from 1985–2015. On that basis, morphological dynamics, including the river’s active channel width, meander’s neck length, water flow length, sinuosity index, and Cornice central angle, were quantitatively investigated. Additionally, the correlation between the stream power and morphological factors was explored using the data adopted from the hydrometric stations. The results show that the dominant pattern of the Karun River, due to the sinuosity coefficient, is meandering, and the majority of the river falls in the category of developed meander rivers. Moreover, the number of arteries reduced in an anabranch pattern, and the river has been migrating towards the downstream and eastern sides since 1985. This phenomenon disposes a change in the future that can be hazardous to the croplands and demands specific considerations for catchment management.