One dominant factor on how well students learn mathematics is the quality of teaching. Studies have shown that typical mathematics classroom is frosted with teaching technique that centered on explain – practice – memorize. There is a paucity particularly in Nigeria. This study therefore, investigated the effect of brain-based learning strategy on the achievement regarding the learning of Mathematics of 522 Senior Secondary School Students in Oyo State, Nigeria. The moderator effect of cognitive style was also examined on independent variable (instructional strategy) and dependent variable (mathematics achievement). The study adopted a pretest-posttest non-equivalent control group design in a quasi – experimental setting. The ANCOVA statistic was used to analyzed the data collected fro the study. The result revealed significant main effect of treatment, (F(1,510) = 75.0; P < 0.05), cognitive style (F(1,510) = 23.78; P < 0.05) and significant interaction effect of treatment and cognitive style (F(1,510) = 5.027; P < 0.05) on achievement in mathematics. The result showed that brain-based instructional strategy enhanced students’ achievement in mathematics more than the conventional lecture method. It is therefore recommended that Teachers of mathematics should adopt the strategy in teaching mathematics in senior secondary school.