In this study, the relationship between self-directed learning (SDL) skills and 21st century skills were investigated. In addition, the role of academic field in the relationship between SDL skills and 21st century skills have been investigated. The research data were collected from a total of 568 teacher candidates with various academic fields. The analysis of the data was carried out using structural equation modeling. In addition, the established model was tested separately for each academic field and the groups were compared. According to the findings, there is a positive and statistically significant relationship between SDL skills and 21st century skills. Moreover, SDL skills are a strong predictor of 21st century skills. According to the group comparisons, SDL skills of students in the special ability academic field do not predict 21st century skills. However, SDL skills of students in other academic fields strongly predict 21st century skills. As a result, it can be said that as the SDL skills increase on the basis of the academic field of individuals, 21st century skills will increase too.