Aeolian-fluvial processes are crucial in shaping landforms. Despite the advancements in understanding the sedimentary processes of aeolian-fluvial interactions, the sedimentary patterns of these interactions are complex in spatiotemporal scale, and the records of Holocene small-scale aeolian-fluvial interaction sedimentary is insufficient, especially in the Tibetan Plateau region. Therefore, this study focuses on analyzing the sedimentary patterns of aeolian-fluvial interactions and their response to climate change in the Paiku Co basin of the southern Tibetan Plateau (TP). Through the examination of aeolian-fluvial sequences, Optically Stimulated Luminescence (OSL) dating is utilized to establish a chronological framework. Furthermore, proxy indices are explored to identify potential sediment models and their reactions to climate change. The findings indicate that fluvial activity predominated during a relatively warm and wet period around 5.1–4.6 ka, while thicker aeolian sands accumulated extensively during 4.6–4.1 ka as the climate transitioned to cold and dry conditions. On a millennial scale, the aeolian-fluvial interaction sedimentation is characterized by alternating deposition of clay layers and medium to fine sand. This sedimentation pattern is predominantly influenced by climate change. Overall, the findings shed light on the complex coupling between aeolian and fluvial processes in response to past climate changes, which has important implications for understanding the landscape evolution and environmental changes in this sensitive high-altitude region.