The study investigated factors influencing elective science students’ perception of their Biology classroom environment in low and high academic achieving senior secondary schools in the Central Region of Ghana. The cross-sectional survey research design was adopted. Participants were 356 third-year elective science students, selection through a multi-stage sampling technique. Data were obtained using the Biology Classroom Environment Questionnaire (BCEQ). This was after the senior secondary schools that offer elective science program had been categorized into low and high academic achieving schools based on their performance in Senior Secondary School Certificate Examination/West Africa Senior Secondary School Examinations for five years. Two third-year intact classes were randomly selected from four schools under each category. Data analysis includes Factor and Item Analyses, and Multivariate Analysis of Variance. The findings revealed that four factors influence elective science students’ perception of their Biology classroom environment. The findings further suggested that elective science students in both school categories had a low perception of their Biology classroom environment but significantly different in favor of the elective science students in low academic achieving schools in teacher support, cooperation, and equity. Implications of the study are discussed and recommendations given.