The watershed system has a complex game relationship between the benign operation and coordinated development of various elements of flood-sediment transportation, eco-environment, and socio-economy (FES). With the increasing breadth, depth, and intensity of human activities in watersheds, it is urgent to coordinate the FES. The relationship of water–sediment in the Yellow River Basin (YRB) is complex, with a prominent contradiction in water supply and a fragile ecosystem. This research tries to build a comprehensive evaluation model for FES and explore the complex interaction between FES in the YRB from 2000 to 2020. The results demonstrated that (1) the comprehensive flood-sediment transportation index (CFTI) and comprehensive eco-environment index (CEI) presented fluctuating growth. In contrast, the comprehensive socio-economy index (CSI) revealed a linear growth trend. The CFTI of Sanmenxia, CEI of Toudaokuan, and CSI of Ningxia had the highest growth rates, with 36.03%, 6.48%, and 107.5%, respectively. (2) FES's positive and negative effects were alternating, with heterogeneity in both time and space. (3) The coupling coordination degree (CCD) in the YRB indicated an increasing trend, ranging from 0.53 to 0.87, from reluctantly coordinated development to good coordinated development. The lagging subsystem was CFTI (2000–2001 and 2008–2020) and CSI (2002–2007), and the CEI was not lagging. (4) Exploratory Spatial Data Analysis (ESDA) demonstrated significant differences in the CCD of the YRB, and areas with similar CCD within the basin tend to be centrally distributed in space. At the same time, there was negative spatial autocorrelation in coordination. The results provide a scientific theoretical and methodological framework for strategic research on the YRB system's governance, protection, and management.