The study examined the effects of instructional simulation strategy on students’ academic performance in Chemistry in Ekiti State secondary schools. This study adopted quasi – experimental pre-test and post-test two group design (one experimental group and one control group). The targeted population for the study consisted of all the Senior Secondary School (S.S.S.) two Chemistry students in public secondary schools in Ekiti State. The sample consisted of 169 SS II students available in the classes that were selected from four public secondary schools in Ekiti State. The sample was selected using multistage sampling procedure. Two instruments were used for this study. These are Chemistry Performance Test (CPT) and Instructional Simulation Package (ISP). The face and content validity of the instrument was ensured by experts of Tests and Measurement and Chemistry Education. The reliability of the instrument (CPT) was determined through test re-test method which yielded reliability coefficient value of 0.819. The study was carried out in three stages namely pre-treatment stage, treatment stage and post-treatment. The data collected for this study were analyzed using descriptive and inferential statistics. All the hypotheses were tested at 0.05 level of significance. The findings of the study revealed that there was no significant difference in the pre-test mean scores of students exposed to instructional simulation and conventional strategies but there was significant difference in the post-test mean scores of students exposed to instructional simulation and conventional strategies. The use of instructional simulation strategy enhanced better performance of students in Chemistry than the conventional method. It was recommended among others that the use of instructional simulation strategy should be encouraged in Chemistry class in secondary schools so as to enhance better academic performance of students in Chemistry. Keywords: Instructional Simulation, Students, Performance, Chemistry,