Improving water management depends on understanding the functioning of irrigation and drainage systems across different environmental scales. For this purpose, this study in the Nile Delta of Egypt particularly examines the spatial and temporal variation of drainage water salinity from the system to the plot level. A better understanding of this variation across nested scales is crucial to refine the government's drainage reuse strategy and reduce the adverse effects on agricultural productivity, lagoon ecology, and human health. The study investigates the drainage system of the Meet Yazid study area (82,740 ha) located in the upper central part of the Nile Delta. The parameters measured were electrical conductivity (EC), dissolved oxygen (DO), pH, and temperature. Results showed that salinity and quality of drainage water in the Nile Delta vary highly with space and time. The secondary drains exhibited the highest variability of salinity compared with main drains and subsurface drainage collectors because they accumulate salts from deeper soil layers and seepage of saline groundwater at the time of low flow discharge. In secondary drains, the salinity increased up to four times that of drainage water coming from the collectors. Moreover, DO values were most of the time not meeting standards for reuse in irrigation, especially at main drains that collect not only agricultural drainage but also untreated household sewage water.