The present investigation endeavored to understand trends in climatic, hydrological, and agricultural variables in the five semi-arid river basins of Maharashtra (India). For this, parametric and non-parametric statistical techniques were applied. The monsoon rainfall over the study area reveals no considerable increase during the past (1981–2013) and future (2020–2050). Although the construction of a large number of impoundment structures during the last two decades resulted in a significant rise in post-monsoon groundwater table (by 40 cm/decade), it caused a decline in surface runoff. The study area witnessed a significant increase in area under irrigated crops at the cost of rainfed crops, which resulted in a significant increase in groundwater withdrawal (GWW) by 70 cm/decade. The cropped area and productivity of irrigated crops heavily depend on rainfall and groundwater resources. Moreover, the Southern Oscillation Index (SOI) has a positive connection with the productivity of irrigated crops. On the other hand, a considerable increase in annual minimum temperature (AMNT), annual maximum temperature (AMXT), and annual mean temperature (AMT) (by 1.02, 0.50, and 0.82 °C, respectively) along with a rise of > 100 mm in potential evapotranspiration (PET) is registered during 1985–2015. The study indicates that the irrigated crops are more vulnerable to heat stress, as PHS (plant heat stress with > 34 °C) days show a considerable increase (2–5 days/decade). Furthermore, the climate projection suggest a significant rise of 1.05 °C in AMT by 2050, which is very likely to intensify the hydro-meteorological droughts and adversely affect the agricultural productivity of rainfed and irrigated crops as well. Briefly, the human-induced changes in cropping patterns (without a considerable increase in rainfall/water resource) from one side and the climatic changes (including extreme events) on the other side may exacerbate the regional water scarcity and food security challenges in the semi-arid region of Maharashtra (India) in the near-term future.