This study investigated the effect of computer based instruction (CBI) on secondary school learners’ academic achievement in Biology. Methodology: The study was carried out in four schools, using quasi experimental research design and was guided by systems theory. The target population was 40, 564 secondary school Biology learners. Sampling was by purposive sampling and simple random sampling. The sample comprised of 161 learners. These were obtained from four form two streams in four secondary schools that had learners of mixed gender. Each secondary school contributed a stream, which gave four intact groups. Data collection was by use of questionnaires and achievement test. The collected data was analysed using descriptive statistics such as frequencies, percentages and means and inferential statistics such as analysis of covariance (ANCOVA) and analysis of variance (ANOVA), using the Statistical Package for Social Sciences (SPSS). The data was then presented in the form of tables and a graph. The significance level of the difference between the variables was done at the alpha value of 0.05. Findings: Findings of the study indicate that learners who were taught using CBI had superior scores compared to those who were taught conventionally. The ANCOVA to explore whether or not there was a statistically significant difference between the groups of learners indicated that indeed there was a statistically significant difference between the groups. Consequently, CBI improves learners’ academic achievement in Biology. However, there was no effect of gender on the way CBI influenced the performance. Unique Contribution to Theory, Practice and Policy: The study was guided by systems theory Schools should therefore enhance computer integration in the teaching and learning process.