Nanofluids consisting of nanoparticles dispersed in heat transfer carrier fluid have received attention over the last view years for their enormous potential to improve the efficiency of heat transfer fluids. This work investigated the synthesis of ZnO nanoparticle-based thermal fluids prepared using a two-step process. Chemical precipitation was used for the synthesis of the ZnO powders, and ultrasonic irradiation was used to disperse the nanoparticles in ethylene glycol as the base fluid. The thermal conductivity enhancement of the nanofluid demonstrated a nonlinear relationship with respect to volume fraction and crystallite size, with increases in the volume fraction and crystallite size both resulting in increases in the measured enhancement. The nanofluids used in conductivity measurements were further employed as the working medium for a conventional screen-mesh wick heat pipe. The experiments were performed to measure the temperature distribution and thermal resistance of the heat pipe. The results showed temperature distribution and thermal resistance to decrease as the concentration and the crystallite size of the nanoparticle increased.