Induced seismicity linked to geothermal resource exploitation, hydraulic fracturing, and wastewater disposal is evolving into a global issue because of the increasing energy demand. Moderate to large induced earthquakes, causing widespread hazards, are often related to fluid injection into deep permeable formations that are hydraulically connected to the underlying crystalline basement. Using injection data combined with a physics-based linear poroelastic model and rate-and-state friction law, we compute the changes in crustal stress and seismicity rate in Oklahoma. This model can be used to assess earthquake potential on specific fault segments. The regional magnitude-time distribution of the observed magnitude (M) 3+ earthquakes during 2008-2017 is reproducible and is the same for the 2 optimal, conjugate fault orientations suggested for Oklahoma. At the regional scale, the timing of predicted seismicity rate, as opposed to its pattern and amplitude, is insensitive to hydrogeological and nucleation parameters in Oklahoma. Poroelastic stress changes alone have a small effect on the seismic hazard. However, their addition to pore-pressure changes can increase the seismicity rate by 6-fold and 2-fold for central and western Oklahoma, respectively. The injection-rate reduction in 2016 mitigates the exceedance probability of M5.0 by 22% in western Oklahoma, while that of central Oklahoma remains unchanged. A hypothetical injection shut-in in April 2017 causes the earthquake probability to approach its background level by ∼2025. We conclude that stress perturbation on prestressed faults due to pore-pressure diffusion, enhanced by poroelastic effects, is the primary driver of the induced earthquakes in Oklahoma.