This study investigates the integration of 21st-century skills into the teaching practices of pre-service teachers during their off-campus experiences. Focusing on essential skills such as critical thinking, collaboration, communication, creativity, self-direction, and the use of technology, this research aims to identify which skills are most effectively applied by pre-service teachers in real-world settings. Data were collected from 370 final-year pre-service teachers using a cross-sectional design and a tailored survey instrument adapted from Ravitz's work. The findings indicate that pre-service teachers most frequently integrated technology use and self-direction into their teaching practices. Conversely, skills such as critical thinking, collaboration, communication, and fostering creativity were less commonly applied. No significant gender differences were found in the application of these skills among pre-service teachers in the Central Region of Ghana. These results reveal insights into the readiness and capabilities of future teachers to integrate essential 21st-century skills into their teaching practices, underscoring the critical role of teacher education programmes in preparing educators for the demands of modern classrooms. The study highlights the importance of continuous professional development and the incorporation of innovative teaching methodologies to enhance educational outcomes.