This study aimed to examine the impact of the 5Es (Engagement, Exploration, Explanation, Elaboration, and Evaluation) instructional strategy on secondary school chemistry students' academic achievement in Calabar, Nigeria. A quasi-experimental design was adopted for this study. The population comprised 2,350 Secondary School (SSII) chemistry students drawn from the Calabar Education Zone, Nigeria, from which a sample of 240 students was identified through proportionate stratified random and judgmental sampling techniques. The data was collected through an instrument called ‘’chemistry achievement test’’ (CAT). Two research hypotheses were stated to direct the study. Data obtained were analyzed using the analysis of Covariance and Multiple Classifications Analysis. Results indicated that learners tutored with 5Es instructional strategy enhanced academic achievement more than those tutored using the conventional method. However, students' gender did not make any impact on their achievement when tutored with 5Es instructional strategy and lecture method. It was concluded that the utilization of inquiring and critical thinking skills when students were tutored using the 5ES instructional strategy would be responsible for their high achievement. It was recommended that the introduction of the 5Es instructional strategy should be implemented from the basic primary science to build the younger scientist minds into more creative, goal-oriented, problem-solving individuals.