The strength of tectonic faults and the processes that control earthquake rupture remain central questions in fault mechanics and earthquake science. We report on the frictional strength and constitutive properties of intact samples across the main creeping strand of the San Andreas fault (SAF; California, United States) recovered by deep drilling. We find that the fault is extremely weak (friction coefficient, μ = ∼ 0.10), and exhibits both velocity strengthening frictional behavior and anomalously low rates of frictional healing, consistent with aseismic creep. In contrast, wall rock to the northeast shows velocity weakening frictional behavior and positive healing rates, consistent with observed repeating earthquakes on nearby fault strands. We also document a sharp increase in strength to values of μ > ∼0.40 over <1 m distance at the boundary between the fault and adjacent wall rock. The friction values for the SAF are sufficiently low to explain its apparent weakness as inferred from heat flow and stress orientation data. Our results may also indicate that the shear strength of the SAF should remain approximately constant at ∼10 MPa in the upper 5–8 km, rather than increasing linearly with depth, as is commonly assumed. Taken together, our data explain why the main strand of the SAF in central California is weak, extremely localized, and exhibits aseismic creep, while nearby fault strands host repeating earthquakes.