Abstract This research investigated pre-service science teachers’ intention to use generative artificial intelligence (AI) in inquiry-based teaching using Azjen’s Theory of Planned Behavior. Quantitative data were collected by means of a survey that was administered to pre-service teachers enrolled for an undergraduate teacher education degree at a South African public university. Thereafter, through interviews, the study investigated how the pre-service teachers explained their intentions to use AI in inquiry-based teaching. The survey results showed that pre-service teachers’ AI literacy, subjective norm, attitude to the use of AI, perceived behavioral control, and perceived usefulness have significant effects on their intention to use AI for inquiry-based teaching. However, pre-service teachers’ concern about generative AI and their perceived skill readiness had no significant effect on their intention to use AI. The findings of the interviews that were presented as themes provided some corroboration of the results of the survey. In exploiting the use of AI to drive inquiry-based teaching, the findings of this study provide some insight into possible enablers and inhibitors in the use of AI for inquiry in the classroom. From a practical perspective, these findings could inform teacher educators on issues they may engage pre-service science teachers when discussing the uses of AI.