Periphyton (viz. algal) growth in many freshwater systems is associated with severe eutrophication that can impair productive and recreational use of water by billions of people. However, there has been limited analysis of periphyton growth at a global level. To predict where nutrient over-enrichment and undesirable periphyton growth occurs, we combined several databases to model and map global dissolved and total nitrogen (N) and phosphorus (P) concentrations, climatic and catchment characteristics for up to 1406 larger rivers that were analysed between 1990 and 2016. We predict that 31% of the global landmass contained catchments may exhibit undesirable levels of periphyton growth. Almost three-quarters (76%) of undesirable periphyton growth was caused by P-enrichment and mapped to catchments dominated by agricultural land in North and South America and Europe containing 1.7B people. In contrast, undesirable periphyton growth due to N-enrichment was mapped to parts of North Africa and parts of the Middle East and India affecting 280 M people. The findings of this global modelling approach can be used by landowners and policy makers to better target investment and actions at finer spatial scales to remediate poor water quality owing to periphyton growth.