The study aimed to determine the comparative effectiveness of context-based and traditional teaching approaches in enhancing student achievement in genetics, problem-solving, science inquiry and decision-making skills, and attitude towards the study of life sciences. A mixed method but essentially quantitative research approach involving a quasi-experimental, non-equivalent pre-test post-test control group design was used for the investigation. A total of 190 students from six grade 11 intact science classes, and their six teachers drawn from the six high schools in Tshwane South educational district in Gauteng, South Africa comprised the study sample. The participating teachers taught a genetics course made up of several themes to students in the control and experimental groups over a 7-week period. Five instruments were used to assess student performance in genetics content knowledge, science inquiry skills, problem-solving and decision-making abilities and attitude towards life sciences. Qualitative data derived from teachers' and students' interview protocols were used to supplement the quantitative data. The results suggest that context-based teaching was significantly better than traditional teaching approaches in enhancing student performance, apart from specific science inquiry skills. Performance differences were strongly associated with the type of contexts used in designing the genetics learning materials, and the context-based teaching model used for implementing the materials.