This study investigated the relationship between entrepreneurship skills and business performance in Kisoro Municipality, Kisoro District, Uganda. The primary objectives were to examine the level of entrepreneurship skills practiced by businessmen, assess the level of business performance, and analyze the connection between entrepreneurship skills and business performance. Data were collected through structured questionnaires administered to a sample of 150 entrepreneurs in Kisoro Municipality. Logistic regression analysis was employed to determine the factors influencing the application of entrepreneurship skills and their impact on business performance. The results of the logistic regression analysis revealed several key findings. Higher levels of education, business experience, entrepreneurial training, and capital investment were significantly associated with the application of entrepreneurship skills, which in turn had a positive impact on business performance. Specifically, entrepreneurs with college education had 2.8 times higher odds of practicing entrepreneurship skills compared to those with lower education levels. Additionally, entrepreneurs who had received formal entrepreneurial training showed a 3.32 times greater likelihood of improving business performance. Non-agricultural businesses, with an odds ratio of 3.00, were significantly more likely to benefit from entrepreneurship skills compared to agricultural enterprises. Capital investment also played a significant role, with businesses that had higher capital showing an increased likelihood of higher performance (odds ratio = 2.22). The study concluded that entrepreneurship skills, particularly when combined with access to education, training, capital, and business experience, are essential drivers of business performance in Kisoro Municipality. Nonagricultural businesses, in particular, tend to outperform agricultural businesses, indicating a need for greater support for these sectors. Recommendations include enhancing educational and training opportunities for entrepreneurs, improving access to financial resources, promoting non-agricultural businesses, and strengthening marketing skills to further boost business performance.