Youth unemployment has become a pressing issue in Uganda that threatens sustained economic growth. This study examined the relationship between youth unemployment and Gross Domestic Product (GDP) in Wakiso district using time series data from 2007 to 2021. A multiple regression analysis was conducted using SPSS and Stata to determine the impact. The results showed that a 1% rise in youth unemployment led to a 0.45% decrease in GDP. Additionally, inflation and population growth were found to negatively influence GDP while remittances had a positive effect. The Pearson correlation coefficient between population size and the unemployment rate was reported as 0.390, indicating a moderate positive correlation between these two variables. This suggested that as population size increases, there tended to be a corresponding increase in the unemployment rate, and conversely, as population size decreases, the unemployment rate tends to decline. The conclusions drawn were that youth unemployment significantly reduces Uganda's GDP. Recommendations provided include boosting technical and vocational skills training, investment in agriculture and SME sectors, as well as population control measures to curb the damaging impact on economic productivity and development.