Background: Studies in biology have shown that students perceive variation and evolution to be difficult areas to learn. This has sparked rote learning of variation and evolution concepts and is evidenced in poor performance in tests involving these concepts. Purpose: In light of the significant role of variation and evolution in a human's acquaintance with themselves and their environment, there is a need to ensure that students possess meaningful learning of variation and evolution rather than learning by rote. Hence, this study investigated if the use of CTCA as an intervention will enhance students' performance in variation and evolution concepts in biology. Sample: The potency of the culturo-techno-contextual approach was tried out in this study with 156 senior secondary two biology students, equivalent to (11th grade) with an average age of 14 years. Design and method: The research design was a quasi-experimental pre-test, post-test non-equivalent group design. Data on meaningful learning was collected using a 35 multiple-choice item test of Meaningful Learning in Variation and Evolution. The reliability coefficient of the instrument was, however, determined to be 0.77. Data collected were analysed using ANCOVA since the random assignment of subjects was not achieved. Results: The 76 students in the experimental group who were taught variation and evolution using CTCA performed significantly better F(1, 134) = 15.40; p < 0.0001] than their control group counterparts (N = 80). Conclusion: The data from this study support the potency of the culturo-techno-contextual approach in bringing about the learning of variation and evolution in a meaningful manner. The implications of these results for teacher education in biology are addressed in the article.