Hydrological and geochemical spatial patterns and temporal trends were analyzed using U.S. Geological Survey (USGS) water quality data collected from 1975 to 1999 along the uppermost 600 km of the Rio Grande in Colorado and New Mexico. Data on discharge, specific conductivity (SC), total dissolved solids (TDS), pH, Ca2+, Na+, Mg2+, K+, HCO3−, SO42‐, Cl−, F−, and SiO2 came from six USGS stations ranging from the Colorado‐New Mexico border to below Albuquerque, New Mexico. Linear regression, Kendall's S, and Seasonal Kendall's S’ were used to detect trends, and ANOVA was used to analyze spatial differences between stations. Statistically significant increasing trends occurred in SC, TDS, Ca2+, Na+, Mg2+, K+, Cl−, and F−in the uppermost reaches, and significant decreasing trends of SC, TDS, Ca2+, Mg2+, K+, HCO3−, and SO42‐occurred at the lower stations around Albuquerque. Both fluoride concentrations and pH values increased at and below Albuquerque over the study period. Discharge data show an increasing trend across all stations. Spatially, data for dissolved substances show generally linear upstream to downstream increases in concentrations in the upper four stations, with several notable nonlinear increases at and below Albuquerque (SC, TDS, Na+, Cl−). Significant increases in pH appear at and below Albuquerque, relative to upstream stations, probably due to improved sewage treatment.