Suspended sediment is a major factor driving biodiversity in sediment-laden rivers. However, the composition of aquatic communities and their diversity responses to sediment-nutrient interactions in large-scale sediment-laden rivers are largely unexplored. This study investigated the distribution patterns of zooplankton communities in the main stream of the Yellow River, China. Samples were collected in 41 sampling sections spanning from the river source to the estuary. Based on the sediment concentration of water samples, the study area was divided into a low-sediment region (region 1) and a sediment-laden region (region 2). A total of 164 species were identified in zooplankton samples, with significantly higher species number and density in region 2 compared to region 1. Non-metric multidimensional scaling and analysis of similarities revealed pronounced differences in zooplankton community composition across regions. Despite the prominent contribution of spatial factors to community variations, environmental filtering played a non-negligible role. Nitrogen nutrients emerged as overarching environmental factors shaping zooplankton communities in region 1. In addition to nitrogen nutrients, total suspended solids and turbidity also strongly affected zooplankton communities in region 2. High sediment load weakened the positive effects of nitrogen nutrients on zooplankton diversity. Notably, the sediment effect did not result in species loss, but led to an earlier nitrogen limitation on community diversity. This study provides mechanistic insight into zooplankton community dynamics in a continental-scale sediment-laden river system, unveiling the response patterns of aquatic communities to suspended sediment.