In this article we analyze the spatial and temporal variations in the seismicity and stress state within the central Denali fault system, Alaska, before and during the 2002 Denali fault earthquake sequence. Seismicity for 30 years prior to the 2002 earthquake sequence along the Denali fault was very light, with an average of four events with magnitude ML ≥ 3 per year. We observe a significant increase in the seismicity rate prior to the MW 7.9 event of 3 November 2002 within its epicentral region, starting about 8 months before its occurrence. The majority of the aftershocks of the MW 7.9 event are located within the upper 11 km of the crust and form several persistent clusters with a few aseismic patches along the ruptured fault. The most active aftershock source is associated with the epicentral region of the earthquake. The overall b-value of the aftershock sequence is 0.96 with the highest b-values within the epicentral region. We estimate that it will take 14 years for the seismicity rate to drop back to the background level. The stress regime across the region varies in space and time. The inferred stress regime prior to the 2002 sequence is predominately strike slip. Along the central part of the rupture zone, the orientations of the least- and intermediate-stress axes are reversed after the 2002 earthquake sequence. The maximum compressive stresses along the Denali fault rotate clockwise by up to 35°; the greatest rotations occur in the area of the rupture step-over from the Denali to the Totschunda fault. The inferred stress regime after the 2002 sequence reflects an interchanging thrusting and strike-slip faulting along the ruptured fault. The thrust faulting is concentrated in the epicentral region of the MW 7.9 event and along the rupture segments showing the largest surface offsets.