Hyporheic exchange has been hypothesized to have basin-scale consequences; however, predictions throughout river networks are limited by available geomorphic and hydrogeologic data and by models that can analyze and aggregate hyporheic exchange flows across large spatial scales. We developed a parsimonious but physically-based model of hyporheic flow for application in large river basins: Networks with EXchange and Subsurface Storage (NEXSS). We applied NEXSS across a broad range of geomorphic diversity in river reaches and synthetic river networks. NEXSS demonstrates that vertical exchange beneath submerged bedforms rather than lateral exchange through meanders dominates hyporheic fluxes and turnover rates along river corridors. Per kilometer, low-order streams have a biogeochemical potential at least two-orders of magnitude larger than higher order streams. However, when biogeochemical potential is examined per average length of each stream order, low- and high-order streams were often found to be comparable. As a result, the hyporheic zone's intrinsic potential for biogeochemical transformations is comparable across different stream orders, but the greater river miles and larger total streambed area of lower-order streams results in the highest cumulative impact from low-order streams. Lateral exchange through meander banks may be important in some cases but generally only in large rivers.