It is crucial to educate students on the basis of science, technology, engineering, and mathematics (STEM) education to develop 21st century learning skills. However, there is little research on the contribution of the attitude towards STEM specific discipline to 21st century learning skills. This study aimed to examine the extent to which students' attitude towards science, technology, engineering, and mathematics (STEM) contributes to 21st century learning skills. Data were collected from 779 students from three primary schools and two secondary schools with the S-STEM questionnaire. Quantitative data were analyzed with structural equation modelling. The results revealed that: (1) students' science attitude, and engineering and technology attitude had positive effects on 21st century learning skills; (2) students' science attitude and mathematics attitude positively affected 21st century learning skills indirectly through the mediating role of technology and engineering attitude; and (3) the school year partially played a moderating role. The finding highlights the importance of valuing STEM attitude across disciplines. In particular, students' engineering and technology attitude is more conducive to improving students' 21st century learning skills. It also suggests the need to pay attention to the changing effect of STEM attitude on 21st century learning skills driven by the school year.