Because of changing climatic conditions, uneven distribution of rainfall occurs throughout India. As a result, dependence on groundwater for irrigation has increased tremendously for industrial and domestic purposes. In India approximately 89% of agricultural demands are met through groundwater. Due to increases in population, demand for groundwater and lack of effective utilization have resulted in rapid depletion of groundwater in most parts of the country. Therefore, quantifying groundwater resources is a serious concern in populated states of India, because it is now difficult to supply enough water to every citizen, and will remain so in the future. Because of difficulties in accessing observation data, researchers have begun to depend on satellite-based remote sensing information to deal with groundwater variations. The present study deals with filling the data gap between Gravity Recovery And Climate Experiment (GRACE) and GRACE Follow On (GRACE FO) missions using multilayer perceptron’s (MLPs) during 2017–2018 to obtain a continuous terrestrial water storage anomaly (TWSA) series from 2003 to 2020 for Telangana state, India. The MLP model performed well in predicting the TWSA, with a correlation coefficient of r = 0.96 between modeled TWSA and GRACE TWSA during the test period. Telangana state observed negative TWSAs (annual) in the years 2003, 2004, 2005, 2009, 2012, 2015, and 2016–19. This TWSA series (2003–2020) was then used to evaluate regional groundwater storage anomalies (GWSAs) in Telangana state, which is considered to be one of the water stress regions in India. The TWSAs were converted to GWSAs using Global Land Data Assimilation System (GLDAS) parameters. The Telangana state experienced decreasing GWSA in the years 2005, 2009, and 2012, and from 2015 to 2019, leading to severe droughts. Groundwater well measurements were obtained from the Central Groundwater Board (CGWB) and converted to GWSA at a seasonal scale. The GWSAs obtained from GRACE (GWSAGRACE) were converted to seasonal values and compared with GWSAs obtained from observation well data (GWSAobs). The performance metrics of r = 0.74, RMSE = 5.3, and NSE = were obtained between (GWSAGRACE) and (GWSAobs), representing a good correlation among them. Over the past decade, Telangana state has significantly relied on groundwater resources for irrigation, domestic, and industrial purposes. As a result, evaluating groundwater storage variations at a regional scale may help policy makers and water resource researchers in the sustainable utilization and management of groundwater resources.