The extent of engagement between students and their teachers, peers, academic and extracurricular activities goes a long way in creating a sense of belonging for students and effectual improvement in their performance in the subject matter. This study investigated the effect of mastery learning instructional scheme (MLIS) on post-basic school students' engagement levels in Mathematics in Osogbo, Nigeria. The purpose of this quasi-experimental study was to determine the effect of MLIS on student affective, cognitive and behavioural engagement in Mathematics based on students' gender and score levels. Two co-educational government senior secondary schools were purposively selected as the study's population, out of which a total of 191 Post-basic School II students from two intact classes were engaged as samples from the two schools. A 31-item Student Engagement Questionnaire (SEQ) was adapted as a research instrument. SEQ was subjected to a reliability test using Cronbach Alpha and the value of 0.73 was obtained. Descriptive statistics and ANCOVA were used to examine data gathered in accordance with the hypotheses. Outcomes of the study among others revealed significant improvement in students' cognitive, behavioural and affective engagement for MLIS class (t [subscript (189)] = 2.68, p < 0.05). Gender had a statistically significant influence on affective (F [subscript (1, 94)] = 2.04, p < 0.05) and behavioural (F [subscript (1, 94)] = 0.77, p < 0.05) engagement. It was concluded that MLIS improved students, cognitive, affective and behavioural engagement in Mathematics. Thus, the study recommended that mathematics teachers should consider using MLIS in teaching Mathematics while taking into consideration students' sitting arrangements with respect to their gender and score levels.