Background - Acute kidney injury is an emerging global public health problem significantly associated with increased in morbidity, mortality, and extra cost incurred. Type 2 diabetes mellitus is an independent risk factor for acute kidney injury that is not well investigated in developing countries including Ethiopia. Objective - To assess the incidence and predictors of acute kidney injury among type 2 diabetes mellitus patients having follow-ups in Amhara region Comprehensive Specialized Hospitals. Methods - Institution-based retrospective follow-up study was conducted among 538 type 2 diabetes mellitus patients from January 1, 2014, to January 1, 2020, by systematic random sampling. Kaplan-Meier curve and Log-rank test were used to compare survival time between different categories of explanatory variables. Cox proportional hazard was used to determine significant predictors and proportional hazard assumptions were checked by plotting cox Snell’s residual and global test. Results - the incidence rate of acute kidney injury among type 2 diabetes mellitus patients was 38 per 10,000 person-months observations. The significant predictors were poor glycemic control [AHR (95% CI) 1.70(1.06, 2.74)], Hypertension [AHR (95% CI) 2.36(1.17, 4.79)], Congestive heart failure [AHR (95% CI) 1.79(1.11, 2.89)], Chronic kidney disease [AHR (95% CI) 2.02(1.23, 3.33)], Dyslipidemia [AHR (95% CI) 2.57(1.40, 4.70)], Diabetic nephropathy [AHR (95% CI) 2.08(1.24, 3.51)], Sepsis [AHR (95% CI) 2.96(1.87, 4.70)] and Body mass index((> 30 & 25-29.9 kg/m2); [AHR (95% CI) 4.24(1.98, 9.07) and 2.84(1.50, 5.38) respectively)]. Conclusion - the incidence of acute kidney injury among type 2 diabetes mellitus patients was relatively higher in this study area than in previous studies. Implementing good glycemic control, close monitoring of comorbidities, infection prevention, and weight reduction were vital to reducing the incidence of acute kidney injury in type 2 diabetic patients.