Interdisciplinary science teaching is an issue in various countries. One example in Europe is Germany, especially regarding comprehensive schools. At the same time, German teacher education is primarily subject-specific. An examination of data on self-efficacy beliefs is helpful for understanding the qualifications of teachers for interdisciplinary science. Previous measurement instruments for teaching biology, chemistry, physics, and science lack a literature-based, theory-based, or curricular-valid measurement or a systematic obstacle to overcome. Thus, to meet these requirements, this research developed a draft for a new instrument to measure self-efficacy beliefs of interdisciplinary science teaching (SElf-ST). As the theoretical base, the instrument operationalizes a model of pedagogical content knowledge for teaching science and adapts it to self-efficacy beliefs. In a cross-sectional study (N = 114 pre-service and trainee teachers), a ten-factor-solution for self-efficacy beliefs resulted from an exploratory factor analysis (Kaiser–Meyer–Olkin-criterion = 0.858, α = 0.70–0.86). Nine factors are linked to the theoretical model. An additional tenth factor emerged: Teaching Ethically Relevant Issues. Nine factors show low and medium correlations with teaching experience. Eight factors show at least low correlations with self-rated content knowledge in no less than one of the three subjects. In general, science-specific factors show rather low or medium correlations, and generic factors (e.g., Applying Media, and Applying Methods of Evaluation) show low or no correlations. This result is in accordance with the context specificity of self-efficacy beliefs. These results meet most of the research expectations and provide initial indications of the concurrent, curricular, and divergent validity of the SElf-ST instrument. The paper argues for the development of a new, theory-based instrument to measure self-efficacy beliefs of interdisciplinary science teaching.