Crop loss due to drought is a complex issue, because it changes according to the drought intensity and duration, and the developmental stage of the plants when drought occurs. In order to assess the drought-induced decline in crop harvest, drought variability and the yield sensitivity of winter wheat, maize, sugar beet, and sunflower to drought during their growing seasons is investigated in the Republic of Moldova. This is then used as an example of the response of non-irrigated crops to increasing drought tendency in south-eastern Europe. The quantification of drought was done by using the standardized precipitation evapotranspiration index (SPEI) at 1- to 12-month lags during the period from 1951 to 2012. The relationship between drought at various time scales and the standardized yield residuals series (SYRS) for individual crops over the country and the Balti chernozem steppe of Moldova (represented by Balti experimental site) for the 1962-2012 farming years were investigated. In order to detect the trends and the shifts in the SPEI time series over 62 years, the non-parametric, Mann-Kendall and Pettitt tests were used for each month of the year to cover the main life cycle of the crops. The trend analysis of agricultural drought emphasizes an increasing trend from June to October, and becomes significant in the southern region at the 95% level during July to September. The SPEI highlights the main periods of dry/wet persistence and the regional characteristics of drought which are present in the Southern region, and make this region more prone to severe drought persistence, mostly during the last decade. Drought during the plant reproductive stages may significantly reduce grain yield potential, the relation between the SYRS and the SPEI explaining up to 62% of the low-yield variability.