This study determined the effect of constructive controversy strategy (CCS) and the moderator effect of self-efficacy on students’ attitude to genetics concepts in Oyo State, Nigeria. The study was anchored to situated learning theory, while the pretest-posttest control group quasi-experimental design was adopted. The sample comprised senior secondary school II science students from six public-owned secondary schools randomly selected from two local government areas using fishbowl without replacement. An intact class of secondary school II science students from each school was randomly assigned to CCS (121) and conventional strategy (119). Data were analyzed using analysis of covariance at p<0.05. There was a significant main effects of treatment on student’ attitude (F_(1;215)=4.42; partial η²=0.02) to genetics concepts. This implies that the observed difference in the attitude mean scores of students to genetics after they were exposed to CCS and control groups was significant. Students taught with CCS had improved attitude (x ̅=65.00) than those in the conventional strategy (x ̅=56.63).  Hence, CCS enhanced students’ attitude to genetics. In terms of interaction, treatment and genetics self-efficacy had significant interaction effect on students’ attitude to genetics (F_{(2; 213)}=3.04; partial η² = 0.05), indicating that self-efficacy of the students influenced the effectiveness of the strategies employed in this study and this will favour medium self-efficacious students whenever these strategies are used. The implication of this is that biology teachers should always consider students’ self-efficacy whenever they want to implement constructive controversy strategy in biology classroom.