As one of the most widely used annular pressure seals, labyrinth seals are used to reduce the fluid leakage between different pressure stages. They are multi-toothed seals with circumferential grooves located on the rotor surfaces and/or stator surfaces, which are distributed along the axial direction. The intricacy of the surface geometry and directionality of the seal pattern assist in converting pressure into dissipated kinetic energy without rotor-stator rub effects. The majority of previous studies focused on annular labyrinth liquid seals with smooth rotor/grooved stator (SR/GS) case, whereas this paper attempts to elucidate the effects of geometric variables modification for smooth stator/grooved rotor (SS/GR) case using Computational Fluid Dynamics (CFD) and design of experiments (DOE) techniques. In this study, a smooth stator/grooved rotor liquid seal was modeled and validated against experimental data. The model was then used as a baseline case for a sensitivity analysis of its geometry variations. Simulation results under different pressures/rotor speeds were used to validate the CFD setup. Four geometric parameters of the seal were then selected as design variables to adapt the baseline geometry for potential performance improvements. The design space was discretized using the DOE technique. Similar mesh/simulation setups were automatically generated for each design point. Regression analysis was applied based on the CFD results for a better understanding of the effects associated with different design variables. These results can be used to improve the current design of smooth stator/grooved rotor annular pressure seals in order to achieve lower leakage rates.