High-resolution Galileo data of Ganymede's complex surface provide strong and ubiquitous evidence of strike-slip motion: en echelon structures, strike-slip duplexes, laterally offset pre-existing features, and strained craters. In a previous study, we performed a detailed mapping of these strike-slip morphologies within nine regions of Ganymede: Dardanus Sulcus, Tiamat Sulcus, Nun Sulci, Byblus Sulcus, Nippur and Philus Sulci, the Transitional Terrain of Northern Marius Regio, Anshar Sulcus, Arbela Sulcus, and Uruk Sulcus. Strike-slip indicators were inferred in various combinations at each site, in addition to extensional processes. However, the prominence of strike-slip indicators suggests shearing has been an important process to the structural development of Ganymede's surface. Moreover, tidal stresses on Ganymede, under particular circumstances, may have been sufficient to induce Coulomb failure and generate strike-slip faulting. Here we investigate the role of both diurnal and non-synchronous rotation (NSR) tidal stresses on Ganymede using the numerical code SatStress. We resolve normal and shear tractions onto discrete fault segments of specified orientation and assess Coulomb failure potential for the nine inferred fault zones. Testing a range of subsurface fault depths (z = 0–5 km) and ice friction (μf = 0.2–0.6), we find that tidal stress models of combined diurnal and NSR stress readily promote Coulomb failure within each studied fault zone. High friction (μf = 0.6) limits failure depths to ∼1 km, while low friction (μf = 0.2) extends failure depths to ∼2 km, consistent with elastic thickness estimates. We also compare each fault zone's predicted shear sense to the inferred shear sense from our structural mapping efforts and find compatible senses of shear among six of the nine regions that exhibit notable fault offset and/or prevalent inferences of en echelon, duplexes, and strained craters. In addition, principal stress orientations and failure feasibility computed on a global scale suggest that combined diurnal and NSR tidal stresses promote Coulomb failure within the shallow (< 2 km) icy lithosphere across much of Ganymede. Coulomb failure is limited near the equator by large compressive NSR stresses, but stresses at mid- to high-latitudes readily promote Coulomb failure along a wide range of fault orientations. Based on these results, we infer that nonsynchronous rotation may have assisted the formation and evolution of strike-slip structures on Ganymede.