Background: Vaccination is essential for controlling the COVID-19 pandemic. However adequate vaccine coverage is a critical to the effectiveness of the vaccine at a population level. Data on to acceptability of the vaccine in Urban areas are limited. This study examined the prevalence, factors associated with willingness to receive COVID-19 vaccine and reasons for hesitancy in the predominantly urban Wakiso district of Uganda. Methods: Data were obtained from a cross-sectional study conducted from March 1st, 2021, to September 30th, 2021 in the urban population-based cohort of the Africa Medical and behavioral Sciences Organization (AMBSO). Multivariable modified Poisson regression analysis was used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals of willingness to accept the COVID-19 vaccine. Results: A total of 1,903 participants were enrolled in the study; 61% of whom were females. About 63% of participants indicated willingness to accept the COVID-19 vaccine. Younger age groups (13-19 and 20-29) were less likely to accept the vaccine compared to the persons ages 40-49 years (aPR=0.79; 95% CI: 0.74, 0.84 for the 13-19 years and 0.93; 95% CI: 0.88, 0.98 for age group 20-29, compared to those ages 40–49 years. Post-primary education (aPR=1.05; 95% CI: 1.02, 1.09 compared to primary level), being a students and government staff (APR=1.13; 95% CI: 1.04, 1.23 compared to construction and Mechanic workers) were associated with willingness to receive COVID-19 vaccine. Some of the reported reasons for hesitancy included; concerns about side effects 154(57.0%), about 64(23.7%) did not think the vaccines were effective, and those who did not like the vaccines 32(11.9%). Conclusion: A substantial proportion of individuals were not willingness to receive the COVID-19 vaccine. More effort is needed to reduce vaccine hesitancy, especially among the young and people with lower formal education.