The seismicity pattern along the San Andreas fault near Parkfield and Cholame, California, varies distinctly over a length of only fifty kilometres. Within the brittle crust, the presence of frictionally weak minerals, fault-weakening high fluid pressures and chemical weakening are considered possible causes of an anomalously weak fault northwest of Parkfield. Non-volcanic tremor from lower-crustal and upper-mantle depths is most pronounced about thirty kilometres southeast of Parkfield and is thought to be associated with high pore-fluid pressures at depth. Here we present geophysical evidence of fluids migrating into the creeping section of the San Andreas fault that seem to originate in the region of the uppermost mantle that also stimulates tremor, and evidence that along-strike variations in tremor activity and amplitude are related to strength variations in the lower crust and upper mantle. Interconnected fluids can explain a deep zone of anomalously low electrical resistivity that has been imaged by magnetotelluric data southwest of the Parkfield-Cholame segment. Near Cholame, where fluids seem to be trapped below a high-resistivity cap, tremor concentrates adjacent to the inferred fluids within a mechanically strong zone of high resistivity. By contrast, subvertical zones of low resistivity breach the entire crust near the drill hole of the San Andreas Fault Observatory at Depth, northwest of Parkfield, and imply pathways for deep fluids into the eastern fault block, coincident with a mechanically weak crust and the lower tremor amplitudes in the lower crust. Fluid influx to the fault system is consistent with hypotheses of fault-weakening high fluid pressures in the brittle crust.