The fluid dynamic and thermal performance of three nanofluids containing aluminum oxide, copper oxide, and silicon dioxide nanoparticles dispersed in 60:40 ethylene glycol and water base fluid as a coolant in a microchannel heatsink are compared here by two methods. The first is a simple analytical analysis, which is acceptable for very low nanoparticle volumetric concentration (1−2%). The second method is a rigorous three-dimensional finite volume conjugate heat transfer and fluid dynamic model based upon a constant heat flux boundary condition, which is applicable for cooling electronic chips. The fluids’ thermophysical properties employed in the modeling are based on empirically derived, temperature dependent correlations from the literature. The analytical and computational results for pressure drop and Nusselt number were in good agreement with the nanofluids showing a maximum difference of 4.1% and 2.9%, respectively. Computations cover the practical range of Reynolds number from 20 to 200 in the laminar regime. Based on equal Reynolds number, all of the nanofluids examined generate a higher convective heat transfer coefficient in the microchannel than the base fluid, while copper oxide provided the most significant increase by 21%. Based on the analyses performed for this study, nanofluids can enhance the cooling performance of the heatsink by requiring a lower pumping power to maintain the same maximum wall temperature. Aluminum oxide and copper oxide nanofluids of 2% concentration reduce the pumping power by 23% and 22%, respectively, while maintaining the same maximum wall temperature as the base fluid.