This study investigated the effect of gender on academic achievement in Science using Mastery Learning Strategy and Conventional Method on Senior Secondary School Students in Nasarawa West Senatorial Zone of Nasarawa State, Nigeria. The quasi-experimental non-randomized pre-test, post-test control group design was used. The study also employed random sampling technique to select 200 (120 male and 80 female) senior secondary school two (SS III) students offering Science from four intact classes. A 53-item Science Achievement Test (SAT) constructed by the researchers and validated by experts in Science education was used to obtain data. After pilot testing the instrument using 80 students from three intact classes, the data obtained were analyzed using Pearson Product Moment Correlation Coefficient statistic where a reliability index of 0.78 was obtained. Data collected were analyzed using descriptive statistics of mean, independent t-test and Analysis of Covariance (ANCOVA). The study revealed that students exposed to learning Science through Mastery Learning Strategy performed better.