River channel dynamics are natural autogenic occurrences for fluvial rivers with influences from human modifications and climatic factors. Remote sensing and geographic information system tools and techniques, aerial photographs, and satellite imagery have been used to determine epochal channel erosion, accretion, and unchanged locations along Tana River, Kenya's longest river. Six reaches within a 142-km Saka-Mnazini stretch were studied by comparing sequential changes in the position of the channel in 1975–1986, 1986–2000, 2000–2017, and 1975–2017 epochs. Manual and automatic digital processing procedures and GIS tools were applied to visualize and quantify the reach-wise spatial and temporal morphological changes. The erosion and accretion channel changes over the study period were observed and quantified at all reaches. Meandering and switching off or abandoning the main active channel was also illustrated. The potential driving forces of morphological changes included varying hydrological regime, upstream land use practices, nature of channel gradient, and riparian vegetation occurrence changes. We found no clear evidence to link river regulation with the river channel dynamics. Results deliver the latest evidence on the dynamics of Tana River. This information is crucial for understanding river evolution characteristics and aid in planning and management at the lower reaches which has remained poorly understood. Use of remote sensing data in concert with GIS provides efficient and economical quantitative spatial and temporal analysis of river channel changes.