Background: The Coronavirus Diseases 2019 (COVID-19) causes a unique threat and a great challenge to chronic disease patients. Apart from its severity for all communities, a chronic disease patient is highly vulnerable to the current COVID-19 pandemic. Therefore, this study aimed to assess preparedness and response against the COVID-19 among chronic diseases patients who had follow-up at healthcare facilities. Methods: An institutional-based cross-sectional study was conducted in the North Shoa Zone from May 5, 2020, to June 5/2020. A pre-tested and semi-structured questionnaire was used to collect data. The study participants were selected by simple random sampling technique. The data were entered into the Epi-data and exported to SPSS for cleaning and analysis. Bivariable and multivariable logistic regressions were used to identify the factors associated with the COVID-19 preparedness and response. Results: A total of 410 (97%) patients were responded to face to face interview administered questionnaire. Nearly two-thirds of the respondents had good knowledge, 54% were well prepared, and 63% had a good response to the COVID-19 pandemic. Male participants, news media (TV & Radio), social media, tuberculosis, hypertension, and diabetes mellitus were significantly associated with a good preparedness. Informal education, news media (TV & Radio), and having hypertension were significantly associated with good response to the COVID-19 pandemic. Conclusion: The prevalence of preparedness and response to the COVID-19 pandemic among chronic disease patients was low. Male participants, source of information, educational status, and having chronic diseases were significantly associated with the COVID-19 prevention preparedness and response. It should be continued to provide awareness creation for chronic patients through news media (TV and radio) and social media to increasing the preparedness and response to the COVID-19 pandemic.