This study examined the impact of a pedagogy that is culturally influenced and laced with technological and contextual elements known as the culturo-techno-contextual approach (CTCA) on promoting knowledge retention of biology concepts. The research design was mixed methods, and the sample consisted of 88 senior secondary school II students selected from two Lagos State educational district V schools in Nigeria. Quantitative data was collected using the Variation and Evolution Achievement Test with a reliability value of 0.79, while qualitative data was collected using the Students' Perception of CTCA Interview Guide. All students in the two sample schools used for the experimental and control groups took a pretest before treatment, a posttest at the end of the treatment phase, and a retention test four weeks later. The ANCOVA output demonstrated a statistically significant difference in knowledge retention [F (1,85) = 134.50; p < 0.05]. This suggests that experimental students retained more.