Diversity-related challenges in the classroom and the abstract nature of some of the biological concepts present significant challenges to achieving educational objectives. This study investigated the effect of multimedia and dynamic classroom integrated instruction (DCII) on secondary school students‘ academic performance in respiration and photosynthesis in Bahir Dar City, Ethiopia. A non-equivalent, quasi-experimental design with a concurrent embedded mixed-methods research approach was employed. Data were collected using self-constructed Biology Achievement Tests (BAT), a standard learning style indicator (visual, auditory, and kinesthetic (VAK)), a Biology Multimedia Attitude Test (BMA), a checklist for classroom observation, and focus group discussions (FGD). Before the intervention, a pretest was conducted to assess whether the experimental and comparison groups were comparable. The results revealed no significant differences in BAT (t (92) =-.248, p = 0.804) and BMA (t (92) =1.037, p = 0.302) between the experimental and the comparison groups before the intervention. Then, after eight weeks of intervention, the results revealed a statistically significant difference in posttest mean scores between the experimental and comparison groups (t (92) = 5.39, p = 0.000), and between the pretest and posttests (t (47) = -17.461, p = 0.000) in the trial group. It indicated that the experimental groups who were taught using multimedia and DCII had higher mean biology achievement scores than the comparison group that was taught using conventional teaching strategies. The two-way ANOVA results indicated that instructional strategy, achiever level, and the interaction effect of these two significantly affected achievements (P<0.05). The achievement level of low, medium, and high achievers was aligned with their background educational status. However, in the posttest, the lower achiever learners increased by 160.5% mean gain score, which is higher than the medium (144.55%) and higher (112.88%) achiever levels, indicating that lower achiever learners benefited more from multimedia and DCII in terms of percentage mean gain scores. From the trial participants, the visual learning style was found to be the most preferred, and the Repeated Measure Analysis of Variance showed no significant difference in mean scores between the VAK learning style groups (F (2,45) = 1.66, p= 0.201), regardless of time, and did not interact with each other (F (1,45) = .463, P = 0.652). The perception of learning respiration and photosynthesis through multimedia and DCII improved in the trial group after the treatment. The results also revealed a statistically significant difference in concept retention between the groups taught using multimedia and