This study examined the effectiveness of art-based learning strategies in improving students’ academic performance in Biology compared with traditional teaching methods. Grounded in Constructivist Learning Theory, the research employed a quasi-experimental design using a non-equivalent control group with pretest–posttest measures. The participants were Grade 10 students from Sagana National High School, assigned to an art-based or a traditional learning group. Both groups were assessed using the same achievement test covering key Biology topics, including the endocrine system, nervous system, feedback mechanisms, reproductive hormones, and protein synthesis. Statistical analysis was used to compare learning outcomes before and after the intervention. Findings revealed that while both groups began with comparable levels of understanding, students exposed to art-based learning demonstrated greater improvement in academic performance in Biology than those taught through traditional methods. Specifically, the computed Cohen’s d of -0.858 indicates a large effect size, suggesting that the art-based learning strategy had a substantial impact on students’ academic performance. The study concludes that art-based learning is an effective instructional approach that enhances student academic performance and supports a deeper understanding of Biology concepts, highlighting its potential value in science education.