Hydrothermal plumes are deep-sea extreme environments that support dynamic microbial metabolisms. Chemoautotrophic production coupled to the oxidation of reduced energy-laden substrates has been considered the primary metabolism in plumes. Recently, sequencing data suggested organic carbon cycling may also be important. However, the biogeochemical fate of organic carbon in hydrothermal plumes remains unconstrained. Here, we used an interdisciplinary approach to investigate the metabolisms of a suite of organic substrates and constrain the impacts of hydrothermal plumes on deep-sea carbon cycling. Acetate and methanol were detected throughout the water column, and both were rapidly metabolized in the Guaymas Basin. Heterotrophic production rates from acetate and methanol, up to 7.69 µg C L-1 d-1, greatly exceeded chemoautotrophic production, often by orders of magnitude. Functional genes encoding enzymes associated with heterotrophic production, such as acetyl-CoA or citrate synthetases, were abundant throughout Guaymas Basin, demonstrating the influence of hydrothermal inputs on deep-sea microbiology. Elevated rates of microbial activity coincided with a distinct plume signature, indicating that microbial communities quickly responded to hydrothermal inputs. Our results illustrated that organic carbon is differentially cycled within hydrothermal plumes, suggesting that heterotrophic production near hydrothermal vents may profoundly impact metabolic activity and carbon cycling in these deep-sea habitats.