The study evaluated the effect of differentiated instruction on the academic performance of senior secondary school students in Islamic studies in Kaduna state, Nigeria. The objectives of the study were to: determine the pre-test and post-test performance of students taught Islamic studies using differentiated instruction and compare the performance of Senior Secondary School students taught Islamic studies using differentiated instruction and those taught using lecture method in Kaduna state. The study was guided by theory of the Zone of Proximal Development (ZPD) by Lev Vygotsky among others. Quasi experimental design was employed. The sample size was one hundred and forty-six(146) respondents selected from four (4) intact classes of senior secondary II students offering Islamic studies from four (4) senior secondary schools of Zaria education zone, Kaduna state. The researcher used purposive sampling technique. After which, the four (4) schools were selected. The schools were categorized into boys, girls and co-educational schools. The researcher took one boys’, one girls’ and two co-educational schools of which two were from urban and rural areas each, within the zone. The study adopted performance test as the sole instrument for the purpose of data collection. The instrument consisted twenty items multiple-choice objective test titled “Islamic Studies Differentiated Instruction Performance Test (ISDIPT) and the reliability index was 0.62. The data collected and analyzed using appropriate statistical tools as contained in the statistical package for social sciences (SPSS):mean and standard deviation were used to respond to the four research questions and paired sample t-test to test the first null hypotheses while independent sample t-test to the other three null hypothesis. The findings showed that the post-test scores of students taught Islamic studies using differentiated instruction is significantly better than pre-test scores; it revealed that students taught Islamic studies using differentiated instruction performed significantly better than those taught with lecture method; it also revealed that students in urban areas taught Islamic studies using differentiated instruction performed slightly better than students in rural areas; and also it finally revealed that students taught Islamic studies using students preferred learning mode performed significantly better than those taught with lecture method in Senior Secondary Schools in Kaduna state. Recommendations were offered in line with the findings.