The ecological assessment of rivers under the Water Framework Directive (WFD) requires the use of biological quality elements (BQEs) across defined abiotic types of rivers. However, limited evidence exists on how well biological indices perform across multiple typological classes, particularly under the influence of complex, overlapping stressors. This study evaluated the diagnostic performance of four biological indices (IO—diatoms, MIR—macrophytes, MMI_PL—benthic macroinvertebrates, and EFI + PL—fish) in 16 river sites in southern Poland. These were classified into four abiotic types (5, 6, 12, and 17) and subjected to varying levels of human pressure. Biological, physical and chemical, and hydromorphological data were collected along environmental gradients including conductivity, nutrient enrichment, and habitat modification. Statistical analyses were used to evaluate patterns in community composition and index responsiveness. The IO and MMI_PL indices were the most consistent and sensitive in distinguishing between reference and degraded river conditions. MIR and EFI + PL were more variable, especially in lowland rivers, and showed stronger associations with habitat structure and oxygen levels. Conductivity emerged as a key driver of biological responses across all BQEs, with clear taxonomical shifts observed. The results support the need to consider both typological context and local environmental variation in ecological classification. The findings underscore the need for typology-aware, pressure-specific biomonitoring strategies that combine multiple organism groups and integrate continuous environmental variables. Such approaches can enhance the ecological realism and diagnostic accuracy of river assessment systems, supporting more effective water resource management across diverse hydroecological contexts.