Anoxia in lakes is a major growing concern. In this study we applied a multiproxy approach combining high-resolution hyperspectral imaging (HSI) pigment data with specific HPLC data to examine the Holocene evolution and main drivers of lake anoxia and trophic state changes. We find that when human impact was low, these changes were driven by climate and natural lake-catchment evolution. In the last 500 years, increasing human impact has promoted lake eutrophication and permanent anoxia.