From 300 BC to AD 300, the city of Pergamon underwent a profound transformation that impacted the rural settlement patterns and the concomitant geomorphodynamics. We present a geoarchaeological study in a long-term settled catchment in the Pergamon micro-region to disentangle the Holocene geomorphodynamics and triggering factors, for example, climate change and human activity. The analyses of eight radiocarbon-dated sediment profiles from the Tekkedere alluvial fan and its catchment indicate four principal sedimentation phases. Phase 1 (ca. 6.2 to 5–4 ka) is dominated by the floodplain aggradation of the receiving Bakırçay River, which is followed by the formation of floodplain soils (phase 2). Substantial geomorphodynamic changes occurred around 4 ka (phase 3), when the edge of the floodplain was buried by fan sediments of the tributary Tekkedere creek. This is attributed to supraregional aridization and rapid climate change events, superimposed by the onset of local human activities. Repeated cycles of coarse- and fine-textured fan sediments with age inversions after ca. 3.8 ka and valley infills younger than 1300 yr BP indicate the strong erosion and redeposition of sediments in phase 4. These increased geomorphodynamics may coincide with the changing settlement pattern and thus reflect human–environment interactions.