Subsurface fluid injections can disturb the effective stress regime by elevating pore pressure and potentially reactivate faults and fractures. Laboratory studies indicate that fracture rheology and permeability in such reactivation events are linked to the roughness of the fracture surfaces. In this study, we construct numerical models using discrete element method (DEM) to explore the influence of fracture surface roughness on the shear strength, slip stability, and permeability evolution during such slip events. For each simulation, a pair of analog rock coupons (three-dimensional bonded quartz particle analogs) representing a mated fracture is sheared under a velocity-stepping scheme. The roughness of the fracture is defined in terms of asperity height and asperity wavelength. Results show that (1) Samples with larger asperity heights (rougher), when sheared, exhibit a higher peak strength which quickly devolves to a residual strength after reaching a threshold shear displacement; (2) These rougher samples also exhibit greater slip stability due to a high degree of asperity wear and resultant production of wear products; (3) Long-term suppression of permeability is observed with rougher fractures, possibly due to the removal of asperities and redistribution of wear products, which locally reduces porosity in the dilating fracture; and (4) Increasing shear-parallel asperity wavelength reduces magnitudes of stress drops after peak strength and enhances fracture permeability, while increasing shear-perpendicular asperity wavelength results in sequential stress drops and a delay in permeability enhancement. This study provides insights into understanding of the mechanisms of frictional and rheological evolution of rough fractures anticipated during reactivation events.