Au mineralization in the western Lupa goldfield, southwestern Tanzania was associated with transpression and reverse sinistral slip along a network of steeply S dipping shear zones with non-Andersonian geometries. Slip was accommodated by: (1) frictional failure and sliding during emplacement of quartz ± Au-bearing veins; and (2) crystal plasticity and fluid-assisted diffusive mass transfer. The Kenge mineral system is situated along a NW-SE-trending shear zone and is characterized by ≤10-m thick, Au-bearing fault-fill veins hosted by well-developed phyllosilicate-rich mylonites. The broadly contemporaneous Porcupine mineral system is situated along an ENE-WSW– to E–W-trending shear zone, which is characterized by narrow, discontinuous mylonitic shear zone within a silicified and nonfoliated granitoid protolith. Au mineralization at Porcupine occurs within steeply dipping fault-fill and subhorizontal extension/oblique-extension veins. Three-dimensional frictional reactivation theory provides a self-consistent explanation for the different vein styles at Kenge and Porcupine and extends the classic fault valve model to the general case of oblique slip along multiple, arbitrarily oriented shear zones. Analysis of the differential stress required for frictional reactivation suggests the following: (1) the Kenge shear zone was intrinsically weaker than the Porcupine shear zone, consistent with the lack of well-developed mylonites at Porcupine; and (2) frictional reactivation of the Kenge shear zone occurred under suprahydrostatic but sublithostatic pore fluid pressures, whereas frictional reactivation of the Porcupine shear zone occurred under near-lithostatic fluid pressures. We hypothesize that near-lithostatic pore fluid pressures relieved effective normal stresses at grain-grain contacts, helping to preserve intragranular and fracture porosity at the Porcupine orebody. As such, these pore spaces may be important microstructural sites for Au mineralization. Low effective normal stresses can also explain the poorly developed phyllosilicate-rich mylonites and limited degree of shear zone weakening at Porcupine.