The study investigated the effects of 5e-cyclic and mental models instructional strategies on junior secondary school students’ academic performance and self-efficacy in Basic Science. The study adopted non-equivalent, pretest-posttest control group quasi-experimental research design. The population for the study comprised all junior secondary school students in Ondo State, Nigeria. The sample size consisted of 95 junior secondary school two (JSII) students in three intact classes. The three (3) classes were assigned randomly to two experimental groups (5e-cyclic-model and mental-model instructional strategies) and one control group (teacher expository method). Two instruments were used for data collection namely: Basic Science Concept Test (BSCT) and Basic Science Self-Efficacy Rating Scale (BSSERS). Data collected were analysed using analysis of covariance (ANCOVA). The results showed that there was a significant effect of treatments on the academic performance of students taught with 5e-cyclic-model and mental-model instructional strategies and teacher expository method with students taught using 5e-cyclic-model and mental model showing better performance than teacher expository. Also, significant effect of treatment was found in the self-efficacy of students taught with 5e-cyclic-model and mental-model with students from both techniques performed better than teacher expository. The study concluded that 5e-cyclic and mental models instructional strategies had improved the academic performance and self-efficacy of students in Basic Science. Therefore, it was recommended that teachers should use 5e-cylic model and mental model instructional strategies to teach Basic Science concepts because the instructional strategies have been demonstrated to be more effective as a teaching-learning strategies for Basic Science than teacher expository method.