Soils in northern latitudes store more than twice the amount of carbon (C) currently in the atmosphere and are warming faster than the rest of the globe. Warming has been linked to an expansion of woody vegetation across tundra, raising questions about how these two phenomena interact to modulate C stocks and turnover. We investigated how long-term warming and litter addition have modified microbial processes, soil characteristics, and C and nitrogen (N) stocks. We hypothesized that warming and litter would interact to amplify soil C losses and would be accompanied by increases in microbial activity. Using soil samples from a 16-year warming and litter addition field manipulation, we measured soil C and N stocks, heterotrophic respiration, extracellular enzyme activity, and microbial stoichiometry. We found that warming decreased C and N stocks across the entire soil profile. Depth-specific analyses illustrated that these changes are driven by increasing microbial activity at 5–10 and 10–15 cm depth, and trends toward higher dissolved organic C and N at 5–10 cm depth. This emphasizes the potential for increased leaching losses with warming and additional litter. While litter addition did not change overall C and N stocks, it appears to modify the ecosystem by adding nutrients and C to the soil. Collectively, these findings highlight the vulnerability of northern soils to continued warming with respect to nutrient and C turnover and provide insights into the mechanistic responses of tundra soil to prolonged global change.