Industrial activity, dam construction, and agriculture—while important for socioeconomic progress—can severely damage the natural environment. To evaluate the effects of these human activities on the bio-integrity of riverine ecosystems, we examined the Wanan reach of the Ganjiang River (Wanan River basin), which contains the river’s largest reservoir. On the basis of 20 attributes of zooplankton, we constructed a zooplankton index of bio-integrity (Z-IBI) evaluation system using range analysis, discriminant analysis, and correlation analysis. Our research found that these anthropogenic activities can greatly change the composition and number of zooplankton community. The overall health status of this catchment was classified as “good”, and the eco-health situation of the reference, industrial, dam-controlled and agricultural sites were deemed “healthy”, “fair”, “good”, and “fair”, respectively. Our results suggested that the three activities adversely affected the integrity of local aquatic ecosystems. Agriculture was the activity most detrimental to the zooplankton community, followed by industrial production and dam construction. Therefore, we demonstrated that the Z-IBI evaluation system can be applied to reservoir–riverine ecosystems. We also provide guidance on the ecological protection, assessment, monitoring and of reservoir–riverine ecosystems and suggest that additional Z-IBI evaluation approaches be further developed in the future.