Major lower limb amputation is a devastating operation most commonly performed for complications of peripheral artery disease or diabetes mellitus. Data suggest that there is a widespread variation in major amputation rates within and between countries. This study aimed to identify key characteristics of patients undergoing this procedure in our region, and to compare our population to the rest of Australia. Secondary analysis was performed to assess differences seen in the Indigenous population. Cases were identified from a prospectively maintained database and medical records were retrospectively reviewed to record relevant clinical information. A literature review was then undertaken to compare our data to other series. A total of 51 major lower limb amputations were performed between January 2015 and January 2017, and the mean age of patients was 59.5 years. Over 70% of patients were diabetic, and one-third required dialysis. Twenty-three patients were identified as Indigenous, and they were significantly younger (54.6 ± 11.4 versus 63.5 ± 15.9 years, P = 0.02) and more likely to be diabetic (91.3% versus 65.2%, P ≤ 0.01) compared to non-Indigenous patients. The most common indication was arterial ulcer or gangrene (52.9%), but Indigenous patients were more likely to have amputation due to sepsis (47.8% versus 7.1%, P < 0.01). Patients undergoing major amputation in Far North Queensland are more likely to be younger and diabetic than Queensland or Australian counterparts. Diabetes and renal disease were especially prevalent in our cohort, with higher rates found in Indigenous patients.