A first-principle based mathematical model is developed in this paper to analyze the meshing losses in involute spur gears operating in high-load and high-speed conditions. The model is fundamentally simple with a few clearly defined physical parameters. It is computationally robust and produces meaningful trends and relative magnitudes of the meshing losses with respect to the variations of key gear and lubricant parameters. The model is evaluated with precision experimental data. It is then used to study the effects of various gear and lubricant parameters on the meshing losses including gear module, pressure angle, tooth addendum height, thermal conductivity, and lubricant pressure-viscosity and temperature-viscosity coefficients. The results and analysis suggest that gear module, pressure angle, and lubricant pressure-viscosity and temperature-viscosity coefficients can significantly affect the meshing losses. They should be the design parameters of interest to further improve the energy efficiency in high-performance, multistage transmission systems. Although the model is developed and results obtained for spur gears, the authors believe that the trends and relative magnitudes of the meshing losses with respect to the variations of the gear and lubricant parameters are still meaningful for helical gears.