The deviation of natural faults from planarity results in geometric asperities and a heterogeneous stress field, affecting the shear resistance and slip behavior. This study numerically examines the effects of macro-scale roughness, local friction, and wear on the evolution of the fault stresses and shear resistance with fault slip. In contrast to previous analytical and numerical studies, our quasistatic simulations allow for slip at the scale of roughness wavelengths, large roughness levels, and fault opening. The simulations indicate that analytical solutions, which predict a linear increase in shear resistance with slip, significantly overestimate the additional shear resistance from roughness, i.e., the roughness drag, at slips larger than several percent of the minimum roughness wavelength. Starting with mated fault surfaces, the average shear resistance on the fault initially rises rapidly, but the rate of increase diminishes significantly as slip increases and the faults open. While initially showing a larger increase in shear resistance than self-similar faults, at large slip, self-affine faults exhibit significantly smaller shear resistance, and the background stresses are bounded without the need for off-fault inelastic deformation. Although smaller than predicted by analytical solutions, the simulation results show that the additional resistance from macro-scale geometrical irregularities is important, enabling rough faults to operate under shear resistance significantly larger than that from local friction only. The impact of macro-scale roughness increases with the roughness amplitude and the friction coefficient, while wear reduces fault stresses and average shear resistance. The combined effect of local friction and roughness is nonlinear, involving a direct contribution to shear resistance from roughness, as observed in prior studies, and an additional contribution from the increasing average normal stress with slip, which amplifies the resistance from friction and becomes more pronounced at large slip.