Time-integrated normalized difference vegetation index (TI NDVI) derived from the multitemporal satellite imagery (1989–1993) was used as a surrogate for primary production to investigate climate impacts on grassland performance for central and northern Great Plains grasslands. Results suggest that spatial and temporal variability in growing season precipitation, potential evapotranspiration, and growing degree days are the most important controls on grassland performance and productivity. When TI NDVI and climate data of all grassland land cover classes were examined as a whole, a statistical model showed significant positive correlation between the TI NDVI and accumulated spring and summer precipitation, and a negative correlation between TI NDVI and spring potential evapotranspiration. The coefficient of determination (R2) of the general model was 0.45. When the TI NDVI-climate relationship was examined by individual land cover type, the relationship was generally better defined in terms of the variance accounted for by class-specific models . The photosynthetic pathway is an important determinant of grassland performance with northern mixed prairie (mixture of C3 and C4 grassland) TI NDVI affected by both thermal and moisture conditions during the growing season while southern plains grasslands (primarily C4grassland) were predominantly influenced by spring and summer precipitation. Grassland land cover classes associated with sandy soils also demonstrated a strong relationship between TI NDVI and growing season rainfall. Significant impact of interannual climate variability on the TI NDVI–climate relationship was also observed. The study suggests an integrated approach involving numerical models, satellite remote sensing, and field observations to monitor grassland ecosystem dynamics on a regional scale.