This study aimed to determine the impact of teacher candidates' 21st-century skills on their professional competence by controlling for gender, grade level, and income status. Three hundred eighty teacher candidates from different classes and departments were selected to participate in the study. The data obtained using the Multidimensional 21st-Century Skills and Professional Competence Scales were analyzed using the structural equation modeling method. The results indicate that teacher candidates' 21st-century skills positively affect their professional competence when controlling for gender, grade level, and income status. The findings emphasize the importance of pre-service teachers for their future careers to have 21st-century skills such as information and technology literacy, critical thinking and problem-solving, entrepreneurship and innovation, social responsibility and leadership, and career consciousness. It has been concluded that teacher training programs should be designed to support teacher candidates in acquiring 21st-century skills and developing their professional competencies.