Background People with pre-existing chronic diseases are more likely to acquire COVID-19 infections, which can be fatal, and die from COVID-19 illness. COVID-19 vaccination will benefit those at a higher risk of developing complications and dying from the disease. This study aimed to determine chronic patients’ willingness to receive a COVID-19 vaccine and the factors that influence their willingness. Method An institutional-based cross-sectional study was conducted among 423 adult chronic patients in the University of Gondar specialized hospital outpatient departments. The participants were chosen using systematic random sampling methods with an interval of 5. Face-to-face interviews were used to collect data from eligible respondents. Epi-data version 4.6 and SPSS version 25 were used for the data entry data analysis. Bivariable and multivariable binary logistic regression analyses were used to evaluate the relationship between the dependent and independent factors. An odds ratio with 95 percent confidence intervals and a P-value was used to determine the association’s strength and statistical significance. Result Out of 401 respondents, 219 (54.6%) with [95% CI (49.7–59.5%)] of study participants were willing to receive the COVID-19 vaccination. Being a healthcare worker (AOR = 2.94, 95% CI: 1.24–6.96), Lost family members or friends due to COVID-19 (AOR = 2.47, 95% CI: 1.21–5.00), good knowledge about COVID-19 vaccine (AOR = 2.44, 95% CI: 1.37–4.33), favorable attitude towards COVID-19 vaccine (AOR = .8.56 95% CI: 4.76–15.38), perceived suitability of the COVID-19 infection (AOR = 2.94, 95% CI: 1.62–5.33) and perceived benefit of the COVID-19 vaccine (AOR = 1.89, 95% CI: 1.08–3.31), were found to be a significant association with the willingness to receive the COVID-19 vaccine among chronic patients. Conclusion This study confirms that around 55% of adult chronic patients were willing to receive the COVID-19 vaccine. Providing health education for chronic patients to emphasize the knowledge and attitude of the COVID-19 vaccine and raise patients’ perceived risk of COVID-19 and the benefit of the COVID-19 vaccine could be recommended to improve their willingness to COVID-19 vaccination.