Science education in the 21st century emphasizes the development of argumentation and critical thinking (CT) skills for socioscientific issues (SSIs), which students can also apply to any subject, such as biology. This study aimed to determine the effect of problem-based learning with metacognitive prompts (M-PBL) on students’ argumentation and CT. This study employed a quasi-experimental design using a pre- and post-test non-equivalent control group. A total of 121 11th-grade students majoring in science and biology participated in this study. Participants were divided into three groups and were tested under different PBL: (1) M-PBL, 23 males and 22 females; (2) H-PBL (high-intensity problem-based learning), 15 males and 20 females; and (3) L-PBL (low-intensity problem-based learning), 26 males and 15 females. Argumentation and CT skills in M-PBL were compared with H-PBL and L-PBL. Results show that students engaging in M-PBL biology learning had higher levels of argumentation and CT skills. Students’ argumentation and CT skills were significantly improved through M-PBL, and thus should be considered by teachers when restructuring lessons in a problem-solving class setting.