Objective This study aims to investigate the factors affecting development of acute kidney injury (AKI) due to severe hypothyroidism. Methods This single-centre, retrospective observational study involved patients with primary hypothyroidism and thyroid stimulating hormone (TSH) levels of more than 50 mIU/L at their review in the endocrinology outpatient clinic, between January 2015 and April 2021. Patients whose medical history and laboratory data were complete were included in the study. Demographic and laboratory data of patients with AKI (case group) and without (control group) were compared. Factors affecting the development of AKI were examined by logistic regression analysis. Results A total of 100 patients, 20 (11 male (M), 9 female (F)) in the AKI (case) group and 80 (23 M, 57 F) patients in control group, were included in our study. The median age of the case group (56 years, interquartile range (IQR) 44.3–68.5) was significantly higher than the control group (49 years, IQR 32.3–60; p = 0.027), and the ratio of males to females was significantly higher in the case group (p = 0.001). Multivariate logistic regression analyses showed that hypothyroidism diagnosed after the age of 60 years (odds ratio (OR) 59.674, 95% confidence intervals (CI) 5.955–598.031; p = 0.001), free triiodothyronine (FT3) < 1.3 pg/mL (OR 17.151, 95% CI 2.491–118.089; p = 0.004) and creatine kinase (CK) > 1000 U/L (OR 1.522, 95% CI 1.602–82.848; p = 0.015) were predictors for the development of AKI due to severe hypothyroidism. Conclusion We recommend close follow-up and monitoring of patients with AKI caused by severe hypothyroidism if aged > 60 years, CK > 1000 U/L or FT3 < 1.3 pg/mL.