This paper analyzes the historical rainfall characterization and drought conditions in two major southern states of India, namely, Tamil Nadu and Karnataka, through estimation of meteorological drought indices, namely, drought index (DI), Palmer drought index (PDI), and standardized precipitation index (SPI). Monthly and yearly rainfall data, including temperature, have been considered for 110 years. Deficient rainfall conditions have been identified and compared using annual rainfall classification thresholds. Annual rainfall variability and trend have been estimated using Mann–Kendall test and Sen’s slope test. Comparative study on results implies that drought characterization using SPI may amply facilitate the standardization of threshold classification for severity and frequency. Based on threshold classification, it is found that Tamil Nadu witnessed on an average 11 years of moderate drought, 4.36 years of severe drought, and 1.32 years of extreme drought conditions with standard deviations of 4.28, 1.87, and 1.63 years, respectively, during the study period, whereas Karnataka witnessed on an average 9.74 years of moderate drought, 3.91 years of severe drought, and 2.30 years of extreme drought conditions with standard deviations of 4.54, 2.04, and 2.21 years, respectively, during the study period. According to the analysis, drought vulnerability in Tamil Nadu was higher than in Karnataka, based on the number of dry and wet years in terms of SPI threshold values and area covered over 110 years. Karnataka was more susceptible in terms of severity. When compared with other indices, analysis based on drought indices indicates that a single variable-based estimation using SPI is easy to assess and may be significant and definitive in terms of decision making for prioritizing drought mitigation measures in the study area in case of inadequate available data for multiple variable-based drought analysis.