In this study, a pre-chamber was designed to form near stoichiometric mixture and provide multiple turbulent flame jets to ignite the lean mixture and accelerate the combustion in the main combustion chamber for a natural gas engine. A CFD simulation was employed to investigate the impact of the pre-chamber nozzle configurations on flow and combustion processes inside the engine, as well as on the performance of the engine. Various configurations were investigated, including orifice number of 4 to 8 and orifice diameter ranging from 1.6 m to 2.9 mm. A non-dimensional parameter, β, was used to characterize the relative flow area of these configurations. The numerical results indicate that, for a given nozzle flow area, among the design of different orifice numbers, the 6-orifice design can obtain the optimal combustion and engine performance. Otherwise, a design of more orifices leads to slower flame penetrating speed in the main-chamber, and the design of less orifices leads to slower circumferential flames propagations in the main-chamber. Moreover, for a 6-orifice pre-chamber, the optimal orifice diameter was found to be 2.0 mm, corresponding to a β value of 0.3. A design of larger diameters leads to slower penetrating for the flame jets and insufficient radial flame propagations in the main-chamber, while a design of relatively smaller orifice diameters leads to insufficient circumferential flames propagations in the main-chamber. Additionally, for the engine performance, all the pre-chamber designs improve the indicated efficiency and reduce the NOx emission. Especially, the design of 6-orifice with diameter of 2.0 mm achieves a 35.0% increase of indicated thermal efficiency and a 78.0% reduction of NOx emission compared to the prototype engine.