The aim of the current research is to identify the impact of droughts on the vulnerability of water resources in the hydrological basin of Lake Karla in Thessaly, Central Greece, using the Standardized Drought Vulnerability Index (SDVI). The Lake Karla basin covers a total area of 1170 km² and has a semi-arid climate. It is an agricultural basin in which water-demanding crops (such as cotton, maize and alfa-alfa) are cultivated. Drought is an extreme weather phenomenon, occurring more frequently recently with significant impacts, such as reduced infiltration and surface runoff. To assess water resources' vulnerability against the drought phenomenon, the SDVI was applied, which is a composite index that integrates all types of droughts (meteorological, hydrological, agricultural, social and economic). The SDVI, with its holistic approach, can be used as a monitoring tool to provide knowledge for the identification of vulnerable areas. The SDVI incorporates Water Supply, Water Demand, Infrastructure, Impact and drought indices, such as cSPI-6 and cSPI-12, as sub-indices. The SPI (Standardized Precipitation Index), based on precipitation data for the years 1960-2018 from nearby stations, was used to identify drought. The conceptual hydrological model UTHBAL was applied for water balance estimation to calculate the Water Supply sub-index. The Water Demand sub-index was estimated mainly based on the demand for irrigation water. For the calculation of the Ιmpact sub-index, the reduction in agricultural production was used with corresponding data for each hydrological year obtained from the Hellenic Statistical Authority. The Infrastructure sub-index was assessed in terms of the actual capacity of the reservoirs (dams) in the Lake Karla basin related to the total water demand. The sub-indices were standardized on a scale of 0-3. When applying the SDVI index to the Karla basin for 30 hydrological years (from 1978/88 to 2017/18), it was found that the index has a value larger than 1.5 for about 15 years, indicating the high vulnerability of the basin.