Rivers are an important component of the global carbon cycle and contribute to atmospheric carbon exchange disproportionately to their total surface area. Largely, this is because rivers efficiently mobilize, transport and metabolize terrigenous organic matter (OM). Notably, our knowledge about the magnitude of globally relevant carbon fluxes strongly contrasts with our lack of understanding of the underlying processes that transform OM. Ultimately, OM processing en route to the oceans results from a diverse assemblage of consumers interacting with an equally diverse pool of resources in a spatially complex network of heterogeneous riverine habitats. To understand this interaction between consumers and OM, we must therefore account for spatial configuration, connectivity, and landscape context at scales ranging from local ecosystems to entire networks. Building such a spatially explicit framework of fluvial OM processing across scales may also help us to better predict poorly understood anthropogenic impacts on fluvial carbon cycling, for instance human-induced fragmentation and changes to flow regimes, including intermittence. Moreover, this framework must also account for the current unprecedented human-driven loss of biodiversity. This loss is at least partly due to mechanisms operating across spatial scales, such as interference with migration and habitat homogenization, and comes with largely unknown functional consequences. We advocate here for a comprehensive framework for fluvial networks connecting two spatially aware but disparate lines of research on (i) riverine metacommunities and biodiversity, and (ii) the biogeochemistry of rivers and their contribution to the global carbon cycle. We argue for a research agenda focusing on the regional scale-that is, of the entire river network-to enable a deeper mechanistic understanding of naturally arising biodiversity-ecosystem functioning coupling as a major driver of biogeochemically relevant riverine carbon fluxes.