Background: Self-care practice is the activity that a hypertensive patient undertakes intending to improve their health. Poor self-care practice leads to uncontrolled hypertension. Therefore, strategies designed to prevent and control hypertension-related death, disability, and morbidity should consider the level of the patient’s self-care practice and risk factors. This study assessed self-care practice and associated factors among hypertensive patients in public health facilities of Harar Town in eastern Ethiopia. Method: An institution-based cross-sectional study was conducted among 398 randomly selected hypertensive patients from 25 March 2019 to 16 April 2019. Pretested structured questionnaires adapted from validated tools were used to collect data from participants using electronic Open Data Kit software through face-to-face exit interview. Data were analyzed by SPSS version 24. Bivariable and multivariable logistic regression analyses were conducted to identify factors associated with self-care practice. Adjusted odds ratio with 95% confidence interval was used to report association and the significance was declared at p-value < 0.05. Results: Level of good self-care practice was 29.9% (95% confidence interval: 25.3% and 34.7%). Age ⩾ 60 years (adjusted odds ratio = 3.4, 95% confidence interval: 1.2 and 9.3), formal education (adjusted odds ratio = 2.3, 95% confidence interval: 1.3 and 4.2), absence of comorbidities (adjusted odds ratio = 1.8, 95% confidence interval: 1.1 and 3.1), adequate knowledge about hypertension (adjusted odds ratio = 4.7, 95% confidence interval: 2.5 and 8.8), good social support (adjusted odds ratio = 2.7, 95% confidence interval: 1.6 and 4.7), and being khat abstainer (adjusted odds ratio = 1.9, 95% confidence interval: 1.1 and 3.5) were significantly associated with good self-care practice. Conclusion: The prevalence of good self-care practice was low. In this study, good self-care practice was significantly associated with age, formal education, comorbidities, knowledge about hypertension, social support, and current khat chewing condition. Regular check-up and follow-up of patients’ compliance with self-management protocol, and more emphasis should be given to identify factors that potentially impeding patients’ adherence to hypertension self-management protocol.