Our study aims to explore the practice of Inquiry-based Science Teaching (IBST) in schools with contextual challenges in Tanzania. The study draws on multiple data sources. Eleven teachers purposively selected were interviewed. Also, out of 11 teachers, seven were observed in their practical sessions. Participants were selected from community secondary schools in Iringa Municipality in Tanzania. We found that IBST is infrequently practised and then mostly at lower levels (conducting activities and drawing conclusions). Our findings indicate that the main contextual challenges for the practice of IBST include the restrictions by the practical examinations and inadequate resources. Findings also suggest opportunities for the practice of IBST in schools with contextual challenges, such as the use of locally available materials for generating students’ investigations and specific questioning techniques referring to local science applications. Thus the design of IBST may need to be adapted to the context of the learner. This may enable the effective practice of the higher levels of IBST even in the presence of contextual challenges.