A single-stage vapor compression refrigeration system becomes inefficient and impractical when the temperature lift between the evaporator and the condenser becomes large. Under the high-temperature lift, different losses in the system increase, and more refrigerant vapor is formed at the end of the throttling process. The authors have attempted to analyze a vapor compression refrigeration system with a dedicated subcooler for high-temperature lift applications using R134a in the main cycle and four low global warming potential (GWP) refrigerants in the subcooler cycle. The modeling of the proposed system has been carried out in Engineering Equation Solver (EES) considering the energy, exergy, and economic aspects for the simulation of the system. The predicted results show that the use of the proposed system is more beneficial from both performance and economic point of view for high-temperature lift. Nearly 27% improvement in both energetic and exergetic performances are noted whereas cost is reduced by 2% when the proposed system is used instead of a typical refrigeration system. Finally, the present investigation concludes that the use of refrigerant R1234ze is much efficient than the other investigated refrigerants due to its low GWP and compressor discharge temperature, in spite of achieving better thermo-economic performances using R152a as subcooler refrigerant.