The Moab fault, a basin-scale normal fault that juxtaposes Jurassic eolian sandstone units against Upper Jurassic and Cretaceous shale and sandstone, is locally associated with extensive calcite and lesser quartz cement. We mapped the distribution of fault-related diagenetic alteration products relative to the fault structure to identify sealing and conductive fault segments for fluid flow and to relate fault–fluid-flow behavior to the internal architecture of the fault zone. Calcite cement occurs as vein and breccia cement along slip surfaces and as discontinuous vein cement and concretions in fault damage zones. The cement predominates along fault segments that are composed of joints, sheared joints, and breccias that overprint earlier deformation bands. Using the distribution of fault-related calcite cement as an indicator of paleofluid migration, we infer that fault-parallel fluid flow was focused along fault segments that were overprinted by joints and sheared joints. Joint density, and thus fault-parallel permeability, is highest at locations of structural complexity such as fault intersections, extensional steps, and fault-segment terminations. The association of calcite with remnant hydrocarbons suggests that calcite precipitation was mediated by the degradation and microbial oxidation of hydrocarbons. We propose that the discontinuous occurrence of microbially mediated calcite cement may impede, but not completely seal, fault-parallel fluid flow. Fault-perpendicular flow, however, is mostly impeded by the juxtaposition of the sandstone units against shale and by shale entrainment. The Moab fault thus exemplifies the complex interaction of fault architecture and diagenetic sealing processes in controlling the hydraulic properties of faults in clastic sequences.