High cutting temperatures are reported in the machining process because of a large amount of generated heat, which reduces the dimensional accuracy and quality of the machined surface. This paper presents a new methodology to design a carbon dioxide (CO2)-based cooling system in which the cooling effect is produced by using the Joule–Thomson effect during machining of Ti-6Al-4V. The finite element method and computational fluid dynamics are used to predict the tooltip temperature in machining, supply conditions of the coolant, and design parameters. The theoretical heat transfer rate of the tool and workpiece is compared with the simulated value to validate the model. After the validation, the turning experiments of dry machining and CO2-cooled machining are performed under constant cutting parameters. In this experimentation, the coolant supply conditions used are taken from the simulation. From the experimental results, it is observed that the CO2 cooling system provides a reduction in cutting temperature (46.66 %), flank wear (10 %), and surface roughness (46 %) compared with dry machining. However, cutting force is increased (about 33.33 %) because of the pressurized CO2 gas focused on the cutting tool.