Science learning self-efficacy could be regarded as a multi-factor belief which comprises different aspects such as cognitive skills, practical work, and everyday application. However, few studies have investigated the relationships among these factors that compose science learning self-efficacy. Also, culture may play an important role in explaining the relationships among these factors. Accordingly, this study aimed to investigate cultural differences in science learning self-efficacy and examine the relationships within factors constituting science learning self-efficacy by adopting a survey instrument for administration to students in the U.S. and Taiwan. A total of 218 university students (62.40% females) were surveyed in the U.S.A, and 224 university students (49.10% females) in Taiwan were also invited to take part in the study. The results of the structural equation modelling revealed cultural differences in the relationships among the factors of science learning self-efficacy. It was found that U.S. students' confidence in their ability to employ higher-order cognitive skills tended to promote their confidence in their ability to accomplish practical work, strengthening their academic self-efficacy. However, the aforementioned mediation was not found for the Taiwanese participants.