Regional groundwater storage changes in Illinois are estimated from monthly GRACE total water storage change (TWSC) data and in situ measurements of soil moisture for the period 2002–2005. Groundwater storage change estimates are compared to those derived from the soil moisture and available well level data. The seasonal pattern and amplitude of GRACE-estimated groundwater storage changes track those of the in situ measurements reasonably well, although substantial differences exist in month-to-month variations. The seasonal cycle of GRACE TWSC agrees well with observations (correlation coefficient = 0.83), while the seasonal cycle of GRACE-based estimates of groundwater storage changes beneath 2 m depth agrees with observations with a correlation coefficient of 0.63. We conclude that the GRACE-based method of estimating monthly to seasonal groundwater storage changes performs reasonably well at the 200,000 km2 scale of Illinois.