The purpose of this study was to compare the achievement of students taught with concept mapping, cooperative learning, 5E learning cycle and lecture methods with the intention of identifying which one among them could be most suitable for teaching Biology. To guide this study, four research questions were raised and tested at 0.05 level of significance. The design of the study was pre-test, post-test, delayed post-test, quasi experimental repeated measures design. The samples of the study consisted of four mixed secondary schools, 259 students and eight Biology teachers. The major findings of the study include: significant effect of the four instructional methods on achievement and retention; students in the 5E learning cycle and cooperative leaning groups significantly outscored those in the concept mapping and lecture groups on achievement and retention tests; students in concept mapping outscored those in lecture group both on immediate achievement and retention tests; students in 5E learning cycle and cooperative learning groups did not significantly differ on achievement and retention tests; males and females in all the four groups did not significantly differ on the achievement tests; and a non-significant interaction effect between sex and method of instruction on achievement. It was concluded that the adoption of either 5E learning cycle or cooperative learning strategies may be appropriate for the teaching and learning of Biology.