Background and objectives: Diabetes mellitus (DM) stands out among the most important public health problems worldwide since it represents a high burden on health systems and is associated with higher hospitalization rates, and a higher incidence of cardiovascular diseases. Amputations are among the most common complications, leading to disability and increasing care costs. This research aims to analyze the prevalence of DM-related amputations, comorbidities and associated risk factors in the diabetic population residing in the State of Espírito Santo, Brazil. Materials and Methods: This is a quantitative, exploratory, cross-sectional study with a time series design and the use of secondary data registered and followed by the system of Registration and Monitoring of Hypertension and Diabetes—SisHiperdia. Results: The sample consisted of 64,196 diabetic patients, out of them, 3.9% had type 1 DM, 10.9% with type 2 DM, and 85.2% with DM coexisting with hypertension. Most were female (66.6%), aged 40 to 59 years (45.6%), and 60 years and older (45.2%). The prevalence of DM-related amputations in the analyzed sample was 1.2% in type 1 DM, 1.5% in type 2 DM, and 2.2% in concomitant DM and hypertension. Higher amputation rates were observed in males in the age group above 60 years in type 1 DM and type 2 DM and were slightly higher in the age groups up to 29 years in DM with hypertension. A higher prevalence of amputation was related to smoking, physical inactivity, acute myocardial infarction (AMI), stroke, chronic kidney disease (CKD), and diabetic foot (DF) in all types of DM. Conclusions: The present study showed a significant prevalence of DM-related amputations. An increased prevalence was evidenced when correlated with smoking, physical inactivity, AMI, stroke, CKD, and DF with significant statistical associations, except for a sedentary lifestyle in type 1 DM.