Over the past decades, overall ecological conditions in the Caspian Sea have deteriorated. However, a comprehensive understanding of lake-wide spatial differences in anthropogenic pressures is lacking and the biological consequences of human impacts are poorly understood. This paper therefore aims at assessing the individual and combined effects of critical anthropogenic pressures on the Caspian Sea ecoregions. First, cumulative pressure scores were calculated with a cumulative environmental assessment (CEA) analysis. Then, the individual contribution of anthropogenic pressures was quantified. Finally, ecoregion-specific differences were assessed. The analyses show that both cumulative and individual pressure scores are unevenly distributed across the Caspian Sea. The most important individual pressures are invasive species, chemical pollution and poaching. This uneven distribution of pressure scores across Caspian Sea ecoregions creates new challenges for future conservation strategies, as different ecoregions usually require different conservation measures.