Background: Comorbid hypertension among people with diabetes is now becoming a worldwide public health problem. Even though hypertension is the most common comorbidity among diabetes populations, studies on determinants of hypertension among diabetes populations are scarce in Ethiopia, especially in Amhara region. So, this research was aimed to fill this gap. Objective: This study was aimed to identify determinants of hypertension among people with diabetes attending chronic follow-up clinics in Amhara region comprehensive specialized hospitals, Ethiopia, 2021. Method: an institutional-based unmatched case-control study was conducted among 476 participants from March 17 to April 18, 2021, in Amhara region comprehensive specialized hospitals. Multistage sampling technique was used to select participants of this study. Data were collected by using interviewer-administered questionnaires, physical measurements, and a checklist. Data was entered into Epi-Data version 3.1 and exported to Statistical Package for Social Science version 21 for analysis. Logistic regression was used to identify variables having significant association at p-value < 0.05 with a 95% confidence interval. Results: A total of 235 cases and 235 controls were participated in this study. The mean age ± Standard deviation for the controls were 60.12 ± 10.387 and median age for case were 60 with interquartile range of (12- 66). Age > 50 years, a lower level of physical activity [AOR = 1.82, 95 % CI (1.00, 3.31], having depression [AOR = 2.00, 95 % CI (1.24, 3.21)], family history of hypertension [AOR = 2.13, 95 % CI (1.34, 3.37)], not attending a diabetic education session [AOR= 1.87, 95% CI (1.18, 2.96)], longer duration of diabetes [AOR= 1.99, 95% CI (1.05, 3.79)] and poor glycemic control [AOR=1.57, 95% CI (1.01, 2.45)] were the significant determinants of hypertension among individuals with diabetes mellitus. Conclusion: In this study, physically inactivity, having depression, family history of hypertension, not participating in diabetes education, duration of DM, and poor glycemic control were determinants of hypertension in diabetes clients. Therefore, as an integral part of diabetes care, health care providers should screen, assess and treat depression, create participants awareness to attend diabetes education, and advise diabetes individuals to engage in physical activity. Key Words: Hypertension, Diabetes Mellitus, Determinants, Ethiopia