Reservoir sedimentation is a pivotal concern in global reservoir management, exerting substantial influence on the long-term functionality, operational efficiency, and environmental sustainability of reservoirs. In this study, we investigated the spatiotemporal variations and influencing factors associated with sedimentation in the Three Gorges Reservoir (TGR) in China, focusing on the flood control storage (FCS) by using measured data from 2003 to 2022. The Sediment Budget Model (SBM) and the Section Topography Method (STM) were used to quantify sedimentation, and Pearson’s correlation analysis was performed to identify key factors affecting sedimentation. Results indicated that sedimentation in the FCS experienced two stages, it initially declined from 2011 to 2016, followed by a gradual increase since then. Sedimentation in the FCS resulted confined to the permanent backwater area, and it displayed a segmented distribution pattern. Although the sedimentation rate showed a decreasing trend since 2013, the heavy flood events in the tributary of the Jialing River could be the major sedimentation risk in the TGR in the future. Sedimentation in the FCS mainly occurred when the flood retention capacity was used during the wet season, and the increase in streamflow and flood retention amount could significantly stimulate sedimentation in the FCS. The current findings not only facilitate the understanding of sedimentation characteristics in the FCS of the TGR, but also benefit sustainable and effective sediment management strategies for other large reservoirs worldwide.