Experiments were conducted to evaluate the thermal entropy generation, frictional entropy generation, and exergy efficiency of reduced graphene oxide (rGO)–Fe3O4–TiO2 hybrid nanofluid flow in a circular tube under laminar flow. The ternary nanoparticles were synthesized using the sol–gel technique and characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), and Fourier transform infrared spectroscopy (FTIR). The stable ethylene glycol-based ternary hybrid nanofluid was prepared and its thermophysical properties, heat transfer, friction factor, and pumping power at various values of particle weight concentrations (0.05–0.2%) and Reynolds number (211–2200) were studied experimentally. Nusselt number, heat transfer coefficient, friction factor, and exergy efficiency augment with increasing values of particle loading and Reynolds number. Results show the thermal conductivity and viscosity increase, as compared to the base fluid, by 10.6% and 108.3% at ψ = 0.2% and 60 °C. Similarly, for ψ = 0.2% and Reynolds number of 1548, and in comparison to the base fluid data, the Nusselt number and heat transfer coefficient enhancement are 17.78% and 24.76%, respectively, the thermal entropy generation reduction is 19.85%, and the exergy efficiency enhancement is 6.23%. At Reynolds number of 221.1, the rise in pressure drop, pumping power, and friction factor is 13.65%, 11.33%, and 16%, respectively, for ψ = 0.2% as compared to the base fluid data. The overall thermal performance of the system is enhanced by 14.32%. New equations are developed for the evaluation of the thermophysical properties, Nusselt number, and friction factor.