The aim of the study was to establish the attitude of students to learning Biology, to examine the academic performance of students in Biology and to compare the attitude of male and female students towards class size. This study investigated the attitude of students to class size and learning Biology. It established the effect of class size on students’ academic performance in Biology in Senior Secondary Schools in Gombi Educational Zone, Adamawa State. The study adopted survey design Three research questions and three hypotheses were postulated. The target population for the study comprised 17, 523 senior public secondary school students in Gombi Educational Zone, Adamawa State, and a sample size of 400 was selected by stratified sampling technique. The research instrument titled “Attitude of Students’ to Class Size and Learning of Biology Questionnaire (ASCSLBQ)” was adapted from Omwirhiren & Faith, 2016. The instrument comprised of 46 items divided into 3 sections. The face and content validity of the instrument was established by two experts in Counselling Psychology and Test and Measurement in the Department of Science Education, Adamawa State University, Mubi. Test-retest method was used to carry out the reliability test and the reliability coefficient was 0.82. The data collected were analyzed using descriptive and inferential statistics which included percentages, mean, Standard Deviation, and Analysis of Variance (ANOVA). The findings revealed that classes are very rowdy because students are too many, making students not hearing the teacher well during lessons, students love Biology as a subject, because they feel at ease in Biology class, feels good when they solve Biology questions, and are willing to spend more time reading Biology books. There is no significant difference between male and female students attitude towards class size. There is significant difference between the male and female students’ attitude towards the learning of Biology; and there is significant difference between male and female students’ academic performance. Biology is a general subject offered by all senior secondary school students, but the classes allocated to them are too small, as a result the classes are overcrowded. Even though the students have keen interest in Biology, they cannot perform practical very well because the teachers cannot give individual attention to the large numbers of students, others cannot even hear him well during lessons because there are no public address systems. This factor could adversely affect students’ academic performance in Biology. Based on this finding it was recommended that number of students in a class should be streamlined to at most 40 students. In addition, government should provide materials for teaching and learning Biology.