Collaborative problem-solving (CPS) competency is critical for 21st century students. However, reports from the Programme for International Student Assessment (PISA) 2015 have revealed significant deficiencies in this competency among young students globally, indicating a critical need for the cultivation of CPS skills. Therefore, it is essential for educators and researchers to examine the factors that influence CPS competency and understand the potential role of CPS in secondary education. The present study aims to investigate the relationship between collaboration dispositions and students’ CPS competency as well as the relationships of CPS competency and inquiry-based science instruction (IBSI) with science achievement using the PISA 2015 data. A total of 408,148 students from 52 countries and economies (i.e., regions) were included in our analysis. Unlike most previous studies that only investigated one country at a time and neglected the multilevel data structure of PISA, this study provided a global view through adopting multilevel modeling to account for the cluster effect at the school and country levels. Our findings revealed that valuing relationship was positively associated with CPS, whereas valuing teamwork was negatively associated with CPS. Furthermore, CPS competency was found to be a dominant and positive predictor of science achievement among all study variables, underscoring the importance of integrating CPS into teaching practices to promote student success in science. Additionally, different IBSI activities show varying relationships with science achievement, indicating that caution should be taken when recommending any specific practices associated with IBSI to teachers.