AbstractNew developments in the area of the Industrial Internet‐of‐Things (IIoT) and Industry 4.0 offer huge potential for a more efficient and flexible industrial production, but are also accompanied by rising system complexity. Consequently, to deal with the increased system complexity, novel approaches, such as reference architectures, are emerging. However, most of these approaches are not yet mature and rather theoretical than ready‐to‐use. Thus, companies need to be provided with frameworks that actively support the transformation of their systems towards Industry 4.0. One of those frameworks has been introduced with Reference Architecture Model Industry 4.0 (RAMI 4.0), which counteracts the mentioned complexity and can be used for various use cases. However, as most of its concepts are too general to be applied directly to actual systems, the need for directly applicable reference architectures emerges. Therefore, this paper proposes a method to derive more detailed reference architectures based on RAMI 4.0 by making use of model‐based systems engineering (MBSE), which target single manufacturing domains rather than the whole industry. Therefore, relevant stakeholders are analyzed and different types of reference architectures targeting their concerns are identified. The resulting reference architectures should be ready‐to‐use for interested manufacturers and thus, enhance the acceptance of RAMI 4.0 as well as improve systems engineering in industrial manufacturing. Finally, the developed reference architecture is evaluated in a proof‐of‐concept case study of a flexible production system.