This study examined the effect of: (1) learning strategy [project-based learning (PjBL) and problem-based learning (PBL)] on the ability of seaweed product diversification; (2) 21st-century learning skills [critical thinking, communication, collaboration and creativity (4Cs)] on the ability of seaweed product diversification; and (3) the interaction between PjBL, PBL and 4Cs on the ability of seaweed product diversification. This study was a quasi-experiment with a 2 × 4 factorial design, namely two learning strategies (PjBL and PBL) × four types of 21st-century learning skills. The research subjects were college students of a public university (n = 70). Data were analysed using the two-way analysis of variance. The results indicated that: (1) there were significant differences in students' ability to diversify seaweed between groups which were taught with PjBL and the one with PBL; (2) there were differences in the ability of students' to diversify seaweed between the ones in the groups with different 21st-century learning skills; and (3) there was an interaction between learning strategies and 21st-century learning skills towards the ability to diversify seaweed products. This study indicates that the implementation of PjBL brings a better effect compared to the implementation of PBL in fostering 21st-century learning skill.