Nitrate (NO3-) is considered to be one of the most prevalent contaminant in groundwater (GW). Owing to its high solubility and mobility, it is prone to leaching through soils with infiltrating water. High NO3-¬ concentration in groundwater is a human health concern particularly for infants. NO3-¬ in GW shows significant spatio-temporal variability which comes from interaction among multiple geophysical factors such as natural and anthropogenic source availability (land use), environmental forcings such as precipitation history, thickness and composition of the vadose zone, types of aquifers (confined or unconfined), aquifer heterogeneity and geology, , etc. The present work seeks to describe the spatio-temporal variability of NO3-¬ at multiple scales in two different hydrogeologic settings- the Trinity and Ogallala Aquifers in Texas at fine (25 km. ×25 km.), intermediate (50 km. ×50 km.), and coarse (100 km. ×100 km.) scales. An entropy-based approach was used to analyze spatial-temporal variability of NO3- within the aquifers. The Hurst exponent was used to evaluate the long-term persistence and trend in the variability of NO3-. A numerical study using Visual MODFLOW was also conducted to verify the effect of different factors on spatial variability of NO3- at multiple scales. Results demonstrated that the spatial variability of aquifer NO3- is controlled by the overlaying soil type, irrigation-pumping activities, and local flow at the small scale and by the complex interactions between rivers and aquifers along with land use at the intermediate scale, and by lithology and geology at the coarse scale. The trends in variability of NO3- show long term persistence at the intermediate and coarse scales. In the Trinity aquifer, mean NO3- has declined slightly within the past decades, however, percent samples in each decade having NO3- higher than 10 mg/L are almost constant during 1940 to 2008. In the Ogallala aquifer, mean NO3- has increased within the past decades, however, percent samples in each decade having NO3- greater than 10 mg/L significantly decreased due to the use of more efficient methods of irrigation in the same time period.