Algal blooms occurrence is increasing around the globe. However, algal blooms are uncommon in dominantly oligotrophic high-altitude lakes. Lake Titicaca, the largest freshwater lake in South America, located at 3809 m above the sea level, experienced its first recorded algal bloom covering a large fraction of its southern shallow basin in March–April 2015. The dominant algae involved in the bloom was Carteria sp. Water geochemistry changed during the bloom with a simultaneous alkalinization in heterotrophic parts of the lake and acidification in eutrophic shallow areas. A decrease in oxygen saturation (from 105 to 51%), and a dramatic increase in hydrogen sulfide (H2S) concentrations (from <0.02 to up to 155 µg∙L−1) resulted in the massive death of pelagic organisms. Such changes were brought by the exacerbated activity of sulfate-reducing bacteria (SRB) in this sulfate-rich lake. Although levels in total mercury remained stable during the event, MMHg % rose, highlighting higher conservation of produced MMHg in the water. Such an increase on MMHg % has the potential to produce exponential changes on MMHg concentrations at the end food web due to the biomagnification process. Our physicochemical and climatological data suggest that unusually intense rain events released large amounts of nutrients from the watershed and triggered the bloom. The observed bloom offers a hint for possible scenarios for the lake if pollution and climate change continue to follow the same trend. Such a scenario may have significant impacts on the most valuable fish source in the Andean region and the largest freshwater Lake in South America. Furthermore, the event illustrates a possible fate of high altitude environments subjected to eutrophication.