This study examined students’ perceptions of teaching, social, and cognitive presence in an online, asynchronous mastery course as they related to interaction and student course satisfaction. The study design used structural equation modeling to examine the relationships. Data was collected from 166 students who were enrolled in an asynchronous online mastery course, which covered information technology literacy skills. The study was conducted over three years using a questionnaire built upon three previously validated instruments: The Community of Inquiry (CoI) Survey (Arbaugh, Cleveland-Innes, Diaz, Garrison, Ice, Richardson, & Swan, 2008), The Noel-Levitz Priorities Survey for Online Learners (Ruffalo Noel-Levitz, 2016) and the Distance Education Learning Environments Survey (Walker & Fraser, 2005). The results of the study included a confirmatory factor analysis and a structural equation model. Results showed that students’ perception of teaching presence had the strongest positive direct effect on student course satisfaction, while cognitive presence was not a significant predictor of course satisfaction. Cognitive presence was a significant positive predictor of interaction. Social presence had a positive effect on interaction, however interaction was not a significant predictor of course satisfaction. In addition, results showed that as students’ perception of social presence increased, their reported course satisfaction decreased. The results of this research enhance the understanding of how the interdependent relationships between teaching, social, and cognitive presence affect one another. This study adds to the literature on asynchronous online learning, mastery-type courses, can serve as a model for analyzing and improving online course design and implementation, and may be used for future research and development in similar contexts.