Single-sex education, also known as single-gender education is the practice of conducting education with male and female students attending separate classes, perhaps in separate buildings or schools. The study on single sex and learner’s academic performance in secondary schools in Kasama sought to determine the extent to which coeducation schools affect male and female students’ academic performance and to establish students’ and teachers’ attitude on effects of sex on the academic performance of learners. To achieve this, the study employed documentary search and analysis on results from 2013 to 2018. The study was guided by the following research objectives; (a) To establish the effects of co- and single sex education on the academic performance of learners in selected secondary schools of Kasama district, (b) To compare learner’s academic performance at co- and single-sex schools in selected secondary schools of Kasama district and (c) To offer recommendations on how to improve the single sex education system in selected secondary schools of Kasama district. The study employed both the qualitative and quantitative methods and a descriptive survey design that sampled head teachers, teachers and pupils. Data was obtained from the respondents by means of interviews and questionnaires. Frequency tables, graphs, figures and pie-charts were used to analyze the qualitative data. Quantitative data were analyzed by the use of the Statistical Package for Social Sciences (version 26) and Microsoft Excel (version 16). The findings reviewed that coeducation context does affect students’ academic performance compared to single-sex schools in the sense that learners in single-sex schools seem to perform better academically. Further, most of the learners and teachers prefer single-sex schools to coeducation schools and the reasons for the dislike of coeducation context include, high level of indiscipline, boys’ offensive behavior towards girls, encouragement of boy-girl relationships that interfere with learning, the fear of girls to participate freely within classroom as well as teachers’ differential treatment of boys and girls in favor of girls. The study therefore recommended that the ministry of education should establish more single-sex schools and convert underperforming co-education schools into single-sex schools.