Surface roughness ubiquitously prevails in natural faults across various length scales. Despite extensive studies highlighting the important role of fault geometry in the dynamics of tectonic earthquakes, whether and how fault roughness affects fluid-induced seismicity remains elusive. Here, we investigate the effects of fault geometry and stress heterogeneity on fluid-induced fault slip and associated seismicity characteristics using laboratory experiments and numerical modeling. We perform fluid injection experiments on quartz-rich sandstone samples containing either a smooth or a rough fault. We find that geometrical roughness slows down injection-induced fault slip and reduces macroscopic slip velocities and fault slip-weakening rates. Stress heterogeneity and roughness control hypocenter distribution, frequency-magnitude characteristics, and source mechanisms of injection-induced acoustic emissions (AEs) (analogous to natural seismicity). In contrast to smooth faults where injection-induced AEs are uniformly distributed, slip on rough faults produces spatially localized AEs with pronounced non-double-couple source mechanisms. We demonstrate that these clustered AEs occur around highly stressed asperities where induced local slip rates are higher, accompanied by lower Gutenberg-Richter b-values. Our findings suggest that real-time monitoring of induced microseismicity during fluid injection may allow identifying progressive localization of seismic activity and improve forecasting of runaway events