This study investigated the effect of class size on students’ academic performance and classroom interaction across selected secondary schools of south Gondar Zone Addis-Zemen and Taitu secondary schools. Descriptive and inferential statistics of correlation analysis were used to analyze the empirical data. Primary data were collected using five point Likert scale questionnaires. 12 sample chemistry teachers were selected through purposive sampling method and all the questionnaires were correctly filled and collected. SPSS (statistical packages for social science) was used to analyze the data collected from the close ended questionnaire. The mean, frequency and percentile of the dependent and independent variables were computed and interpreted. And also the Pearson correlation coefficient (r) was used to determine the relationship between class size and students achievement measured by students grade nine score out of 100 in 2020 academic year. It was found that large class size adversely affected the students’ academic achievement and class room interaction. It was also observed that class size has negatively affected the teachers’ instructional strategies and students’ psychological readiness which impede students’ academic achievement. But small class size found paramount to improve students’ academic achievement and class room interaction as well as the teachers teaching strategy and students psychological readiness to learn passionately. The Pearson correlation coefficient (r) of the study found out large class- size has a negative effect on students’ academic achievement (r = -1.00) and small class size has a positive effect on students’ academic achievement at (r =1.00). It was interpreted that if class size increases, the students’ academic achievement decreases. Reduction of class size on the contrary revealed the ultimate improvement of students’ academic achievement in chemistry. It was recommended that the community, parents and as well as stake holders should work together to build complementary classrooms and fulfill all the required infrastructural facilities in the schools. The Government further more should increase budget allocation to improve schools and recruit teachers to suit the number of students.