Excess nutrient inputs are a major cause of aquatic ecosystem impairment worldwide. Increased total phosphorus (TP) and total nitrogen (TN) concentrations can lead to eutrophication affecting ecosystem functioning and environmental services provided by streams and rivers. Establishing numeric nutrient criteria is a strategy to reduce nutrient inputs into freshwater ecosystems. Our objective was to estimate nutrient concentrations that could be used as guides to establish nutrient criteria for TP and TN in the Grijalva basin, Mexico. We applied the frequency distribution method to water quality monitoring data for subregions (upper, middle, and lower Grijalva) and for the whole basin, considering two stream size categories. Nutrients were also compared among subregions, land uses, and stream sizes. Agriculture and urban areas showed higher nutrient concentrations than other land uses, probably due to the use of fertilizers and inputs of domestic and industrial wastewater. Higher nutrient concentrations were found in the middle Grijalva and in low-order streams. Nutrient concentrations at the 75th percentile for the reference sites were higher than those obtained at the 5th, 16.7th, and 25th percentiles for the general nutrient data, probably due to the high level of human disturbance in the Grijalva basin. Nutrient concentrations at the 25th percentile are probably too high to protect the aquatic ecosystems in the basin, while concentrations at the 5th percentile can be too restrictive for the basin. Based on our results, nutrient concentrations at the 16.7th percentile are proposed as a first approximation for nutrient criteria to protect river systems in the Grijalva basin.