1. Inbreeding and herbivory can interactively reduce the performance of flowering plants. Here, we investigated whether the magnitude of plant inbreeding depression increases under herbivory as a result of diminished leaf metabolic responses to herbivory in inbreds, which entails increased herbivore growth and feeding damage. We additionally explored whether genetic differentiation among native and invasive plant populations impacts the magnitude and direction of these inbreeding × herbivory interactions. 2. Inbred and outbred plants from eight European (native) and eight North American (invasive) populations of Silene latifolia were exposed to two consecutive control or herbivory treatments (infestation with larvae of Mamestra brassicae). After the first treatment, leaf metabolic responses to herbivory were assessed with untargeted metabolic fingerprinting using UHPLC‐ESI+‐QTOF‐MS/MS. After the second herbivory treatment, herbivore growth and plant feeding damage were assessed. Moreover, plant performance traits were recorded four weeks after the second herbivory treatment. 3. Metabolic fingerprinting revealed that changes in the pool sizes of various metabolic features in response to herbivory were less intense in inbred than outbred plants from native and invasive populations. While herbivore growth and feeding damage were largely unaffected by plant breeding status in invasive populations, herbivores consumed greater biomass from, but showed reduced growth on inbred than outbred native plants. The magnitude of inbreeding depression in plant performance traits was not affected by herbivory, but was partially higher in invasive compared to native populations. 4. Synthesis: The chemical analyses suggest that inbreeding compromises herbivory‐induced metabolic defenses in S. latifolia, while results for herbivore growth and feeding damage indicate that inbreeding simultaneously reduces the nutritional quality of plants. Furthermore, our findings demonstrate that the magnitude and direction of these inbreeding effects can be shaped by genetic differentiation in metabolic responses among native and invasive plants. These range‐specific responses highlight the need to investigate multiple populations with different evolutionary histories to gain a deeper understanding of inbreeding × herbivory interactions and provide novel insights into the role of these interactions in invasion success.