With the intensification of human activities, nitrate pollutants in groundwater are receiving increasing attention worldwide. Especially in the arid Nile Delta of Egypt, groundwater is one of the most valuable water resources in the region. Identifying the source of nitrate in groundwater with strong human disturbances is important to effective water resource management. This paper examined the stable isotopes (δ 15N/δ 18O-NO3 and δ 2H/δ 18O-H2O) and the hydrogeochemical parameters of the shallow groundwaters in the arid southeast of the Nile Delta to assess the potential sources and transformation processes of nitrate under severe urban and agricultural activities. The results revealed that the groundwaters were recharged by the Nile River. Meanwhile, the infiltration of irrigation water occurred in the west, while the mixing with the deep groundwater occurred in the east regions of the study area. The TDS, SO4 2−, NO3 −, and Mn2+ concentrations of groundwaters (n = 55) exceeded the WHO permissible limit with 34.6%, 23.6%, 23.6%, and 65.5%, respectively. The NO3 − concentrations in the shallow groundwaters ranged from 0.42 mg/L to 652 mg/L, and the higher levels were observed in the middle region of the study area where the unconfined condition prevailed. It extended to the deep groundwater and eastward of the study area in the groundwater flow direction. The δ 15N-NO3 and δ 18O-NO3 values suggested that the groundwater NO3 − in the west and east regions of semi-confined condition were largely from the nitrification of soil organic nitrogen (SON) and chemical fertilizer (CF). In contrast, wastewater input (e.g., domestic sewage and unlined drains) and prevalent denitrification were identified in the middle region. The denitrification might be tightly coupled with the biogeochemical cycling of manganese. This study provides the first report on the groundwater NO3 − dynamics in the Nile Delta, which generated valuable clues for effective water resource management in the arid region