To analyze the trends and persistence of nitrate-N in groundwater at multiple spatio-temporal scales, we developed and used an entropy-based method along with the Hurst exponent in two different hydrogeologic settings: the Trinity and Ogallala Aquifers in Texas at fine (2 km × 2 km), intermediate (10 km × 10 km) and coarse (100 km × 100 km) scales. Results show that nitrate-N exhibits long-term persistence at the intermediate and coarse scales. In the Trinity Aquifer, overall mean nitrate-N has declined with a slight increase in normalized marginal entropy (N ME) over each decade from 1940 to 2008; however, the number of hot spots has increased over time. In the Ogallala Aquifer, overall mean nitrate-N has increased with slight moderation in N ME since 1940; however, the number of hot spots has significantly decreased for the same period at all scales.