The livelihoods of poor people living in rural areas of Indus Basin Irrigation System (IBIS) of Pakistan depend largely on irrigated agriculture. Water duties in IBIS are mainly calculated based on crop-specific evapotranspiration. Recent studies show that ignoring the spatial variability of factors affecting the crop water requirements can affect the crop production. The objective of the current study is thus to identify the factors which can affect the water duties in IBIS, map these factors by GIS, and then develop the irrigation response units (IRUs), an area representing the unique combinations of factors affecting the gross irrigation requirements (GIR). The Lower Chenab Canal (LCC) irrigation scheme, the largest irrigation scheme of the IBIS, is selected as a case. Groundwater quality, groundwater levels, soil salinity, soil texture, and crop types are identified as the main factors for IRUs. GIS along with gamma design software GS + was used to delineate the IRUs in the large irrigation scheme. This resulted in a total of 84 IRUs in the large irrigation scheme based on similar biophysical factors. This study provided the empathy of suitable tactics to increase water management and productivity in LCC. It will be conceivable to investigate a whole irrigation canal command in parts (considering the field-level variations) and to give definite tactics for management.