District Cooling Plants (DCP) is the sustainable way of energy consumption, refrigeration, and supply of chilled water to end-users via chillers and distribution networks. Thermodynamic assessment of the vapor absorption refrigeration (VAR) in the open literature has been performed for cooling capacity well below the actual requirement (less than 300 kW) of DCP. Therefore, this work aims to investigate energy and exergy analysis of large-scale single effect VAR cycles operated on NH3-water and water-LiBr systems for a cooling capacity of 4000 kW and assess several operating parameters’ influence on cycle performance. Different parameters such as evaporator operating pressure (water-LiBR = 0.010–0.020 atm, NH3-water = 5.39–6.20 atm), chilled water outlet temperature (288–297 K), absorber temperature (300–305 K), condenser temperature (310–315 K), cooling output (2900–4000 kW) and heat input (4300–5500 kW) to the generator are varied during the parametric analysis. The exergy destruction analysis of the cycle’s components is also included in the study. Overall, the COP (0.89) and Exergy efficiency (89%) of water-LiBr were found to be higher than that of an equivalent NH3-water system which is 0.697 and 81%, respectively. The maximum exergy destruction was found at the absorber unit (24%), followed by the generator (23%). Furthermore, the NH3-water and water-LiBr simulations were optimized for different parametric conditions, and optimal operating conditions were identified for large-capacity district cooling systems. Therefore, the findings will provide the roadmap for designing and optimizing large-scale DCP operated on VAR cycles.