The low enrolment and poor academic achievement of female students in Geography compared to their male counterparts in secondary schools of Ganye Educational Zone necessitated this study. Studies have it that the instructional strategies adopted by Geography teachers in teaching could interact with gender to influence students’ academic achievement. To this end, the study investigated the Effect of Gender on Senior Secondary School Students’ Academic Achievement in Geography when Mastery Learning Strategy and Conventional Method are used for instruction. The quasi-experimental non-randomized pre-test, post-test control group design was used. The study also employed the multi-stage random sampling technique at four levels to select 207 (120 Male and 87 Female) senior secondary school two (SS II) students offering Geography from six intact classes in six co-educational secondary schools in Ganye Educational Zone in Nigeria. A 40-item Geography Achievement Test (GAT) constructed by the researcher and validated by experts in Geography education was used to obtain data. After pilot testing the instrument using 89 students from two intact classes, the data obtained was analyzed using Pearson product moment correlation coefficient statistic. 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 Female students exposed to learning Geography through Mastery Learning Strategy performed better than their Male counterparts. A significant interaction effect of treatment and gender on students’ achievement in Geography was also observed. It was recommended that Geography teachers should re-assess their classroom instructional strategies used in teaching and adopt that which will give the students equal opportunities to excel in Geography.