Channel changes are receiving growing interest in relation to the relevant implications for river management and restoration. In this kind of analysis, purely qualitative approaches have been gradually replaced by quantitative approaches aimed at reconstructing the temporal variations in parameters (e.g., channel width and depth) to investigate not only the evolutionary trend of the river but also the possible cause-effect connections. This paper investigates the channel dynamics in the Basento River (Basilicata Region, Italy) over the past 150 years, when the river was heavily affected by human activities (e.g., hydraulic interventions and gravel mining) and climate changes. Channel adjustments were analysed with historical maps, aerial photos, and geomorphological surveys. The results show that the channel underwent a strong narrowing during the twentieth century, similar to many rivers in Italy, with the most intense phase from the 1950s to the 1990s (with the width varying from −30% to −80%). The morphology pattern remained almost completely unchanged, apart from a few reaches located in the hilly area that were affected by intense modifications before the 1940s. The causes of channel adjustments were identified as human disturbances (land use variations, channel interventions at the reach scale, sediment mining) from the end of the 1800s to present, as well as natural factors (changes in frequency, duration, and intensity of flood events), whose effects have intensified since the late 1990s.