The study’s main purpose was to establish the influence of job satisfaction as a mediator in the correlation between career development and talent retention among teaching staff in Uganda’s private and public universities. Quantitative, correlational and cross-sectional research approaches were used to achieve the study objectives. 341 respondents from the four selected universities were considered. Data was analyzed and presented using a copyright-licensed SPSS tool based on the study’s guiding objectives.  The correlation results revealed that career development, job satisfaction and talent retention are significantly correlated. The Medigraph tests revealed that employees' satisfaction with their current job partially mediated the association between career development and the retention of academic staff. The findings of this study are important to University management, the Ministry of Education, policy makers in enhancing the retention of talented academic staff in the education sector. It is observed by the researchers that this is the opening investigation conducted to identify the mediating effect of job satisfaction in examining the link between career development and retention of skilled and experienced academic staff using empirical evidence from universities in Uganda’s education sector. This study adds to the existing body of knowledge by making an extensive support on the relationship between career development and talent retention of the teaching staff in universities of Uganda. Additionally, it demonstrates that job satisfaction partially transmits the effect of career development on talent retention in Ugandan universities.