This paper investigated the effect of Game-Based Learning on Students’ Interest in Basic Science in Calabar Education Zone, Cross River State of Nigeria. Pretest-posttest quasi experimental research design was adopted in this study. One research question and one null hypothesis guided the study at .05 level of significant. Multistage sampling procedure was employed in this study to select 118 JS3 students from the population of 2,184. The study instruments were Basic Science Achievement (BSAT) and Basic Science Interest Scale Questionnaire (BSISQ).  Kuder Richardson formula 20 and Cronbach alpha reliability estimates of .65 and .72 were reached respectively. Data collected were analyzed using mean, standard deviation and ANCOVA. The results have it that there is a significant effect of teaching methods on students’ interest in Basic Science. Based on the findings, conclusion was drawn and recommendations made; some of which is Game-based among other innovative teaching methods like concept maps, jigsaw cooperative and problem-based learning should be encouraged among teachers of Basic Science to enable students improve on their academic interest and achievement.