Hydraulic conductivity is a basic property of rocks and soil, and its estimation varies as a function of the scale and purpose of the study. This work combines geomorphological analysis, geological data, and groundwater investigations from literature to assess large-scale anisotropies in hydraulic conductivity in the North China Plain. The study area encompasses 144,000 km² and represents the most important groundwater system of China, affected in the last 40 years by severe groundwater depletion, pollution, and subsidence. The investigation area is at the center of a massive groundwater project, the South to North Water Transfer Project, which was designed and implemented to alleviate water scarcity and facilitate environmental recovery. A conceptual model based on geomorphological evidence, supported by borehole logs, and satellite image analysis is used to assess the hydraulic conductivity anisotropies at the regional scale. The model divides the alluvial plain into four geomorphological zones with similar hydraulic conductivity characteristics. Along the general groundwater flow direction, upstream hydraulic conductivity is assumed isotropic but strong anisotropies are deduced downstream. An accurate hydraulic conductivity assessment is essential to improve quantitative studies of contaminant transport, artificial aquifer recharge, and land subsidence in the North China Plain and elsewhere.