Climate change and atmospheric deposition of nitrogen affect biodiversity patterns and functions of forest ecosystems worldwide. Many studies have quantified tree growth responses to single global change drivers, but less is known about the interaction effects of these drivers at the plant and ecosystem level. In the present study, we conducted a full-factorial greenhouse experiment to analyse single and combined effects of nitrogen fertilization (N treatment) and drought (D treatment) on 16 morphological and chemical response variables (including tissue δ13C signatures) of one-year-old Fagus sylvatica seedlings originating from eight different seed families from the Cantabrian Mountains (NW Spain). Drought exerted the strongest effect on response variables, reflected by decreasing biomass production and increasing tissue δ13C signatures. However, D and N treatments interacted for some of the response variables, indicating that N fertilization has the potential to strengthen the negative effects of drought (with both antagonistic and amplifying interactions). For example, combined effects of N and D treatments caused a sevenfold increase of necrotic leaf biomass. We hypothesize that increasing drought sensitivity was mainly attributable to a significant reduction of the root biomass in combined N and D treatments, limiting the plants’ capability to satisfy their water demands. Significant seed family effects and interactions of seed family with N and D treatments across response variables suggest a high within-population genetic variability. In conclusion, our findings indicated a high drought sensitivity of Cantabrian beech populations, but also interaction effects of N and D on growth responses of beech seedlings.