The 2004 Mw 6 Parkfield, California, earthquake was preceded by a 4‐year period of anomalously high seismicity adjacent to, but not on, the San Andreas fault. The rate of small events (Mw<3) at distances between 1.5 and 20 km from the fault plane and at depths >8 km, increased from 6 events per year prior to 2000 to 20 events per year between the 2000 and the 2004 earthquake. This increase in seismicity coincided with an increase in the rate of nonvolcanic tremor, which, if tremor is indicative of creep on the fault plane, suggests that creep may have driven the enhanced seismicity. Coulomb stress‐transfer calculations predict the observed spatial pattern of the seismicity, and thus support a causal relation between creep at the base of the fault zone and off‐fault seismicity. In particular, an observed southeast‐striking lineation of enhanced seismicity is shown to be a direct consequence of a deepening boundary between the crust and mantle southeast of Parkfield, as evidenced by a deepening of the tremor and low‐frequency earthquakes. Other evidence for a causal link between deep creep and off‐fault seismicity is the observation that off‐fault seismicity before and after the 2004 earthquake occurred in the same location. This is expected if the foreshocks are driven by an episode of deep creep and the aftershocks are driven by afterslip, both occurring on the same deep extension of the fault plane.