This study was carried out to examine the effects of computer assisted instruction (CAI) on students’ academic performance in biology in Lagos State using secondary school students in Shomolu Local Government Area. To achieve this objective, three research questions and three research hypotheses were formulated to guide this study. The data was collected from both primary and secondary sources. The primary data were collected with the help of a well-structured questionnaire of two sections administered to the secondary school students in Shomolu Local Government Area of Lagos State. The collected data were analyzed using simple percentages and tables to analyze research questions and Chi-square statistical tool was used for testing of research hypotheses. A structured questionnaire was used as the major instrument for data collection from the secondary school students in Shomolu Local Government Area of Lagos State. After the careful analysis of the data, the following findings were revealed that; there is a significant relationship between computer assisted instruction and students’ academic performance in biology; there is a significant effect of the use of computer assisted instruction on students’ retention in government and there is a significant relationship between the use of computer assisted instruction and students’ participation in lessons. The study concluded with some recommendations that school administrators should demonstrate interest in embracing and using information and communication technology facilities for computer-assisted instruction in all subject areas.