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Objectives Several studies have shown not only a high prevalence of fatigue but also a reduction in health-related quality of life (HRQoL) in patients with rheumatic diseases. Owing to insufficient research in this area, we aimed to assess the prevalence of fatigue and its contribution to impairment of HRQoL in patients with Takayasu arteritis (TAK). Methods This single-centre case–control study included 53 TAK patients who were matched by age, BMI and sex with 100 healthy individuals. Aside from the patients’ general data, the following information was collected: disease activity, level of activities of daily living (HAQ), physical activity levels and chronic fatigue. Results The TAK patients and healthy individuals were comparable in terms of current age, BMI and sex distribution. The median disease duration of TAK was 13.0 (7.0–20.0) years, and 11 (20.8%) patients had active disease. Compared with healthy individuals, patients with TAK had a higher prevalence of fatigue and lower HAQ score, physical activity level and intensity, and physical and psychosocial domains of the modified fatigue impact scale (P Conclusion TAK patients have a higher prevalence of fatigue, which affects different aspects of the disease, including physical function. Thus, fatigue-focused treatments should also be considered in clinical practice. Trial registration The Brazilian Clinical Trials Registry (ReBEC), https://ensaiosclinicos.gov.br/, RBR-9n4z2hh.