Rivers are dynamic systems whose water quality varies significantly across space and time, shaped by the interplay of natural processes and anthropogenic pressures. Spatial variation arises from differences in land use, hydrology, geology, and pollutant source distribution along a river continuum, while seasonal variation is driven by climatic patterns, hydrological cycles, and temporally variable human activities. Understanding these variations is essential for safeguarding ecosystem health, ensuring water security, and guiding effective management interventions. This review synthesizes global evidence on spatial and seasonal patterns in anthropogenically impacted rivers, exploring the mechanisms driving variability, the influence of human activities, and the water quality parameters most affected. It also evaluates methodological approaches for assessing these patterns, including statistical analyses, modelling frameworks, and monitoring strategies, while highlighting their implications for adaptive management and policy development. The study emphasizes that addressing spatial and seasonal water quality challenges requires integrated strategies that combine landscape management, environmental flow regulation, real-time monitoring, and stakeholder engagement, underpinned by robust scientific evidence. Future research priorities include the development of high-resolution, multi-parameter datasets, predictive modelling under climate and land use change scenarios, and comparative cross-basin analyses to inform context-specific solutions. By linking science, policy, and practice, river management can be made more adaptive, targeted, and resilient, ensuring the protection of aquatic ecosystems and sustainable use of water resources.