As science educators seek innovative methods to engage students, the Culturo-Techno-Contextual Approach (CTCA) has emerged as a promising strategy, particularly for African students. CTCA is a culturally responsive teaching method that integrates culture, technology, and locational context, making science more relatable and meaningful. We assessed CTCA's effectiveness in enhancing critical thinking in biology among 121 senior secondary students in Lagos State. An explanatory sequential design was used, with the experimental group taught using CTCA and the control group receiving traditional instruction. Data were collected using the Critical Thinking Test in Nutrition (a = 0.80) and interviews. Results showed a significant improvement in critical thinking for the CTCA group (F(1, 198) = 11.43; p < 0.05), with no significant gender differences (F(1,49) = 0.49; p > 0.05). Students responded positively to intervention, leading to the conclusion that CTCA effectively enhances critical thinking in biology; hence, adoption of CTCA in biology instruction is recommended.