The Oued Souf free aquifer located in the South East of Algeria represents the main water resource used mostly for urban and agricultural activities. The intensive use of chemical fertilizers has led to serious environmental problems such as contamination of the free aquifer in the region. Thus, aquifer vulnerability has been assessed using several different methods (DRASTIC, GOD, and the Susceptibility Index ‘SI’) based on a geographic information system (GIS). For each method, two vulnerability maps have been developed in the years 2002 and 2012. These maps show that the study area is more exposed to urban, and especially agricultural, pollution. Two classes of vulnerability (moderate and high) have been identified by both DRASTIC and GOD methods. A combined analysis reveals that the moderate class showing 48% (for the GOD method), and the high class showing 57% (for the DRASTIC method) are the most dominant. However, the Susceptibility Index method (SI) revealed that the vulnerability varies from moderate to very high-level classes. In 2012, about of 53% of the study area was dominated by moderate vulnerability classes. The high vulnerability class also includes a considerable part of the land (41%) around urban or strongly agricultural areas, while only 6% is under very high vulnerability groundwater contamination. In addition, a marked decrease in the vulnerability level was noticed in 2012 compared to 2002. This decrease is mainly due to the lowering of the water table after the installation of a vertical drainage network to evacuate the surplus water to the depression and Chotts areas in the North of the region. These results provide a guide for decision-makers involved in the protection of groundwater pollution in such a vulnerable area.