The lack of widespread commercialization of High-Temperature Proton Exchange Membrane Fuel Cells (HT-PEMFC) is primarily due to their poor performance and durability. Various factors impact the performance of fuel cells, one such crucial factor being the operational parameters. Suitable operating conditions not only enhance the output cell performance but also extend a fuel cell’s life. Current research on the impact of operational factors on HT-PEMFC performance is largely qualitative in nature, with no quantitative indication of affecting the sensitivity of these parameters. In the present work, a three-dimensional, non-isothermal HT-PEMFC model developed earlier is used to investigate the influential sensitivities of five crucial operating parameters, each with four different levels, and is analyzed quantitatively using six evaluation indexes. The orthogonal/Taguchi method L16(45) is implemented to investigate the impact of operating parameters quantitatively. Further, the effect of each operating parameter on evaluation indexes under different operational current density regimes is investigated. The findings show that, of the parameters chosen, the working temperature and cathode pressure are the most sensitive to cell voltage and cathode overpotential distribution under all operating current density regimes. The findings would provide more precise recommendations for experimental research targeted at improving cell performance by optimizing operational parameters.