We aimed to systematically review and quantify risk factors for first-ever diabetes-related foot ulcer (DFU). Four English and three Chinese electronic databases were searched for cohort and case-control studies reporting risk factors for first-ever DFU. Two researchers independently screened titles, abstracts and full text, extracted data and assessed the quality of included studies. Meta-analyses were performed for risk factors reported in at least two studies, using unadjusted odds ratios and standardised mean differences for dichotomous and continuous variables. Of 6736 potential studies screened, 23 were included in the meta-analysis and 24 in the systematic review. Twenty-eight significant risk factors for first-ever DFU were identified, including older age, obesity, male gender, unmarried status, alcohol consumption, current smoking, insufficient physical activity, longer diabetes duration, increased HbA1c, fasting plasma glucose, creatinine and triglyceride, decreased eGFR and high-density lipoprotein, high vibration perception threshold, albuminuria, low ankle-brachial pressure index ratio, cardiovascular, cerebrovascular and peripheral artery disease, retinopathy, nephropathy, neuropathy, myocardial infarction, foot deformity, skin dryness, insulin treatment and anti-hypertensive treatment. This study provides the first comprehensive synthesis of risk factors for first-ever DFU. Identifying high-risk individuals based on these factors can enhance early intervention strategies, reducing the burden of DFU in diabetes management.