This dataset was generated to understand the impact of 21st-century skills on the teaching performance of secondary school teachers in Sekondi-Takoradi, Ghana. The motivation behind creating the dataset lies in recognizing that these skills significantly affect teachers' effectiveness in integrating them into the teaching and learning process. The study's objectives were twofold: firstly, to identify specific essential skills within the broader category of 21st-century skills that play a significant role in predicting teachers' implementation performance, and secondly, to explore potential gender differences in the application of these skills among secondary school teachers.