In recent years, Inquiry-Based Science Education (IBSE) has emerged as one of the most effective and beneficial science teaching practices for developing science concepts in learners and for motivating them in the study of science subjects. IBSE is a pedagogical practice that allows learners to develop key scientific ideas and to understand the natural world, using skills employed by scientists. Like most science school curricula around the world, the South African life sciences national curriculum (referred to as Curriculum and Assessment Policy Statement - CAPS), advocates for the adoption of IBSE. Despite the growing consensus about the cognitive and motivational benefits of IBSE, this pedagogical approach is seldom implemented by life science teachers, due to various factors. This qualitative research, involving a case study, explored the knowledge, perceptions, and adoption of IBSE by four life sciences high school teachers, conveniently selected from public schools around Johannesburg, in South Africa. Data were collected using semi-structured interviews, and the findings show that participating teachers have substantial knowledge and positive perceptions of IBSE. However, they are less inclined to adopting IBSE in their life science classrooms due to inhibiting factors. We recommend the training of life sciences teachers in effective way of abating the constraints of implementing IBSE effectively.