Burgeoning demand for machinability, health, and ecology, Environmental Protection Agency (EPA) regulations are pushing the modern manufacturing sector to apply dry or biodegradable cutting fluids, which are insufficient in the machining of difficult-to-cut materials. Therefore, this study is devoted to proposing a newly developed hybrid ethanol-ester oil lubri-coolant for machining titanium alloy. To encompass the effectiveness of the proposed cutting medium, the thermophysical properties (density, thermal conductivity, viscosity, specific heat), and tribological properties (friction coefficient, friction force), and investigated. Besides, the machinability performance of hybrid lubri-coolant is determined in terms of cutting temperature, cutting force, surface roughness, residual stresses, tool wear through minimum quantity lubrication (MQL) system in the high-speed machining of heat-treated Ti-6Al-4V. The machinability performance of hybrid lubri-coolant are compared to dry cuttings. Findings have depicted that density, viscosity, and thermal conductivity were decreased with the increase of temperature while specific heat was increased with the increase of temperature. Tribological characteristics showed the highest friction coefficient and friction force under dry conditions while minimum under hybrid ethanol-ester oil (1:1) conditions. The hybrid ethanol-ester oil lubri-cooling in milling showed lower cutting temperature, cutting force, surface roughness, residual stresses, and minimum tool wear results. The hybrid ethanol-ester oil is biodegradable, providing efficient cooling with the evaporation of ethanol, and lubrication due to long-chain ester oil molecules. The polar nature of ethanol and ester oil prevented microparticles adhesion and made a tribo-film on the tool-workpiece and prevented rubbing or frictional heat generation.