Project-Based Learning (PBL) is increasingly recognized as an effective approach for enhancing both students’ academic achievement and social skills. This study examines differences in academic achievement in biology and social skills among high school students in Yangon and Pyin Oo Lwin, Myanmar. Yangon school implemented Project-Based Learning (PBL), whereas the Pyin Oo Lwin school employed traditional teaching methods. A descriptive comparative design was adopted, involving 120 Grade 10 students, with 60 selected from Yangon and 60 from Pyin Oo Lwin. Academic achievement was measured using monthly biology test scores, while social skills were assessed via a researcher-developed questionnaire covering five indicators: positive interdependence, interaction activity, individual responsibility, interpersonal relationships, and group member interactions. An independent samples t-test revealed significantly higher biology scores in Yangon (M = 75.80, SD = 5.97) than in Pyin Oo Lwin (M = 68.10, SD = 6.21; t = 7.01, df = 118, p < 0.01). A Mann–Whitney U test indicated significantly stronger collaboration scores in Yangon (93.5%, SD = 1.60) compared to Pyin Oo Lwin (91.7%, SD = 1.70; U = 577.00, p < 0.05). A Pearson correlation analysis showed a statistically significant, moderate positive relationship between academic achievement and social skills (r = 0.47, p < 0.001, r² = 0.22), indicating that the two variables share only about 22% of common variance. Given the descriptive comparative design, these findings indicate that PBL implementation is associated with higher academic achievement and stronger social skills among Yangon students, rather than directly causing these outcomes. The results underscore the need for equitable access to active learning methodologies across Myanmar's diverse regional contexts.