Face stability is one of the key considerations for safe construction during earth pressure shield tunnelling. Both dynamic excavation of cutterhead and spatial variability of soil are widely reported to notably affect face stability. This study therefore proposed a three-dimensional random large-deformation computational framework to explore the combined effect of these two factors on face stability, via the coupled Eulerian–Lagrangian technique and Monte Carlo simulations. The findings demonstrate that incorporating excavation process improves face stability for small opening ratios but diminishes it for large opening ratios. Moreover, the cutterhead excavation process weakens face stability while soil spatial variability will further reduce face stability. This emphasizes the necessity to concurrently account for the effects of cutterhead excavation and soil spatial randomness in the design of chamber pressure. Finally, a factor of safety-based method is proposed for predicting the chamber pressure, which accounts for both effects of cutterhead excavation and soil spatial randomness. The capability and advantages of the implemented method in estimating the chamber pressure are further demonstrated by the simplified sample developed from a real tunnel project.