This study on effect of think-pair-share strategy on academic performance of senior secondary ii students in chemistry in Benue State was guided by three research questions and three corresponding hypotheses. It employed Quasi-experimental design of non-randomized pre-test, post-test control group design. Population consisted of 1,960 (1,105 male and 855 female) Senior Secondary II (SS2) students in 183 in schools. A sample of 86 (46 male and 40 female) SS II students offering Chemistry in two intact classes were obtained using purposive and simple random sampling techniques. Chemistry Performance Test (CPT) was developed by the researchers for data collection. Face and content validation of CPT was done by three experts and yielded a reliability coefficient of 0.84. Data collection was done by the researchers, aided by research assistants teaching Chemistry. Research questions were answered using mean and standard deviation while hypotheses were tested with Analysis of Co-variance at 0.05 alpha levels. It was found that: significant difference exists in performance of students taught Chemistry using Think-Pair-Share strategy (F (1, 83) = 268.308; p = 0.000 < 0.05). However, no significant difference exists between the performance of male and female students taught Chemistry using TPS strategy (F (1, 42) = 0.381; p = 0.541 > 0.05). It was concluded that TPS strategy is capable of enhancing the academic performance of students in Chemistry, irrespective of gender. Based on findings, it was recommended among others that Chemistry teachers should use TPS strategy to enhance teaching and learning to enhance students’ performance in Chemistry.