Serpentinite has been tectonically entrained into several faults of the San Andreas System that are characterized by creep. Meters-wide zones of serpentinite-rich fault gouge are proposed to have risen buoyantly from deeply buried sources along creeping sections of the San Andreas and Bartlett Springs Faults, and other serpentinite-lined faults in Northern California may have similar origins. The core samples of the two creeping traces recovered from the San Andreas Fault Observatory at Depth (SAFOD) drillhole near Parkfield provide an unparalleled view of ongoing alteration and deformation processes within the San Andreas Fault at ~2.7 km depth. Here we show that examination of the SAFOD core and outcrops of serpentinite within other creeping faults yields information about the mineralogical and chemical changes and the deformation mechanisms that are operative over a range of depths and slip rates. Deformation appears to be concentrated within the serpentinite bodies both during and after their incorporation into the faults, with only limited damage to the adjoining wall rocks. The high solubilities and dissolution rates of serpentine minerals in crustal groundwaters promote solution-transfer creep processes during shear. Serpentine minerals reprecipitate in the early stages of faulting, but serpentine is replaced by other Mg-rich minerals over time as a result of metasomatic exchange between the ultramafic fault rocks and the (meta)sedimentary wall rocks. The predominant exchange mechanism is by diffusional mass transfer, at a scale of millimeters to centimeters, that occurs between serpentine minerals and fragments of crustal rocks entrained in the gouge. Minor Mg-metasomatism of the adjoining wall rocks is concentrated along microfractures. The extent of reaction increases with increasing depth and slip rate, the higher shearing rates enhancing alteration by more thoroughly mixing and reducing the grain sizes of the ultramafic and crustal materials. The secondary mineral assemblages are dominated by Mg-rich phyllosilicates that range from saponite (with calcite) at shallow depths to talc and chlorite (with tremolite) near the base of the seismogenic zone.