The effects of climate change and overexploitation are being strongly perceived in the studied area and the springs discharge is obviously affected. In this paper, Ras El Ain spring discharge and precipitation were analyzed by normalized methods on an yearly timescale. The deficit of Ras El Ain spring discharge due to overexploitation factors and drought effects was estimated. Cumulative drought analyses were carried out using SPI10 and SQI10. Finally, the decreasing trends of the spring discharge due to the deficiency in rainfall were analyzed. The main results reveal that the annual mean deficit of Ras El Ain spring discharge due to overpumping was between 32 and 45%, whereas, annual mean deficit related to drought was between 22 and 35% on average, during the last 30 years (post-1984). The moving averages of SPI and SQI delineate very well the drought periods during last three decades. The cumulative droughts using SPI10 and SQI10 reveal that wet period (pre-1984) with positive values was characterized by high precipitation and spring discharge. Overexploitation period (1984–1989) is distinguished by decreasing SQI10 values whereas, SPI10 is almost stable. The response of the karst system to the precipitation signal has been changed, during the drought period (1990–2000), and the spring behaviour has been modified due to the first overexploitation period. Finally, overexploitation period (2001–2008) is related to the second phase of groundwater intensive pumping for irrigation purposes. Consequently, this period is completely catastrophic causing the drying up of the spring. The decreasing trends analyzed using DPI and DQI showed annual decreasing rates relative to the mean values of −0.268% and −0.105%, respectively. Thus, the results of theoretical model reveal that precipitation will decrease by about DPI=−20.7% and the discharge will decline by about −9.2% by 2050. Consequently, the declining discharge due to climatic variation under natural conditions as pre-1984 was about 10%. Whereas, the catastrophic drying up of the spring was probably the consequence of the anthropogenic effects. Accordingly, it requires the development of sustainable water resources management program to reduce long-term drought risks, restore the groundwater reservoir and minimize the overexploitation effects on spring discharge.