This study aimed to examine the influence of a culturally adapted and context-specific technique of instruction called the culturo-techno-contextual approach (CTCA) on lowering student anxiety and fostering meaningful learning in difficult biology concepts. A quasi-experimental pre-test and post-test non-equivalent group design was used for this study. Data collected from 88 senior secondary school II (11th grade) biology students in education district V, Lagos State, Nigeria on the biology concept of variation and evolution that was perceived to be highly difficult showed that: (a) those students who were taught variation and evolution using the culturo-techno-contextual approach (experimental group; N = 45) had a significantly lower level of anxiety than the comparison group (N = 43); and (b) the students in the experimental group that employed the culturo-techno-contextual approach in the teaching process performed significantly better on the test of meaningful learning in variation and evolution Overall, the findings validated CTCA's efficacy as a treatment for anxiety and fostering meaningful learning of variation and evolution – a historically feared subject in biology. The ramifications of these findings for education and future research are discussed.