Regional fault structures along rift basins play a crucial role in focusing fluid circulation in the upper crust. The major Toro-Bunyoro fault system, bounding to the east of the Albertine Rift in western Uganda, hosts local fluid outflow zones within the faulted basement rocks, one of which is the Kibiro geothermal prospect. This major fault system represents a reliable example to investigate the hydrogeological properties of such regional faults, including the local structural setting of the fluid outflow zones. This study investigated five sites, where current (i.e., geothermal springs, hydrocarbon seeps) and fossil (i.e., carbonate veins) fluid circulation is recognized. This work used a multidisciplinary approach (structural interpretation of remote sensing images, field work, and geochemistry) to determine the role of the different macroscale structural features that may control each studied fluid outflow zones, as well as the nature and the source of the different fluids. The local macroscale structural setting of each of these sites systematically corresponds to the intersection between the main Toro-Bunyoro fault system and subsidiary oblique structures. Inputs from three types of fluid reservoirs are recognized within this fault-hosted hydrogeological system, with "external basin fluids" (i.e., meteoric waters), "internal basin fluids" (i.e., hydrocarbons and sediment formation waters), and deep-seated crustal fluids. This study therefore documents the complexity of a composite hydrogeological system hosted by a major rift-bounding fault system. Structural intersections act as local relative permeable areas, in which significant economic amounts of fluids preferentially converge and show surface manifestations. The rift-bounding Toro-Bunyoro fault system represents a discontinuous barrier for fluids where intersections with subsidiary oblique structures control preferential outflow zones and channel fluid transfers from the rift shoulder to the basin, and vice versa. Finally, this work contributes to the recognition of structural intersections as prime targets for exploration of fault-controlled geothermal systems.