The study investigated the effect of utilization of Instructional materials on students’’ academic performance in Biology in Calabar South Local Government Area of Cross River State. Ex -post- factor research design was adopted for the study. A sample size of (200) Students’ was used for the study and two research instruments tagged; Instructional Materials Questionnaire (IMQ) and a Biology Achievement Test (BAT) was used to gather data for the study. Three research questions in form of null hypotheses were formulated to guide the study. Data collected were analyzed using Pearson product moment correlation coefficient. Results of the study showed that, Availability of Instructional materials in schools enhances students’ academic performance; A significant relationship exist between accessibility of Instructional materials and students’ academic performance; Also, the use of Instructional materials for teaching in schools enhances students’ academic performance. Based on the findings, the major recommendations were, parents should provide for their wards relevant Instructional materials needed for study in school. Instructional materials should be made accessible in schools. Finally, teachers should be well trained on the usage of Instructional materials in schools.