Context: Global change, including land-use change and habitat degradation, has led to a decline in biodiversity, more so in freshwater than in terrestrial ecosystems. However, the research on freshwaters lags behind terrestrial and marine studies, highlighting the need for innovative approaches to comprehend freshwater biodiversity. Objectives: We investigated patterns in the relationships between biotic uniqueness and abiotic environmental uniqueness in drainage basins worldwide. Methods: We compiled high-quality data on aquatic insects (mayflies, stoneflies, and caddisflies at genus-level) from 42 drainage basins spanning four continents. Within each basin we calculated biotic uniqueness (local contribution to beta diversity, LCBD) of aquatic insect assemblages, and four types of abiotic uniqueness (local contribution to environmental heterogeneity, LCEH), categorized into upstream land cover, chemical soil properties, stream site landscape position, and climate. A mixed-effects meta-regression was performed across basins to examine variations in the strength of the LCBD-LCEH relationship in terms of latitude, human footprint, and major continental regions (the Americas versus Eurasia). Results: On average, relationships between LCBD and LCEH were weak. However, the strength and direction of the relationship varied among the drainage basins. Latitude, human footprint index, or continental location did not explain significant variation in the strength of the LCBD-LCEH relationship. Conclusions: We detected strong context dependence in the LCBD-LCEH relationship across the drainage basins. Varying environmental conditions and gradient lengths across drainage basins, land-use change, historical contingencies, and stochastic factors may explain these findings. This context dependence underscores the need for basin-specific management practices to protect the biodiversity of riverine systems.