This study was designed to evaluate (a) the frequency of fatigue and its multi-dimensional nature, and (b) its association with demographic variables, disease-specific variables, and other variables, covering depression and sleep disturbance in patients with ankylosing spondylitis (AS). Sixty-two patients with AS were included in the study. Fatigue was assessed by the fatigue item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Multidimensional Fatigue Symptom Inventory—Short Form (MFSI-SF). While the disease activity was evaluated by the BASDAI, the functional state was assessed by Bath Ankylosing Spondylitis Functional Index, metrological measurements by Bath Ankylosing Spondylitis Metrology Index, global well-being by Bath Ankylosing Spondylitis Global Score, the pain on rest by VAS (0–10 cm), sleep disturbance by Pittsburgh Sleep Quality Index, and depressive symptoms by Zung Self-Rating Depression Scale. Fifty percent of the patients had severe fatigue. Multi-dimensional assessment with MFSI-SF enabled us to identify fatigue in more detail. The disease-specific variables, covering pain, stiffness, disease activity, and physical functioning, contributed significantly with both BASDAI fatigue and MFSI-SF as dependent variables, accounting for 61.3% and 44.7% of the variance, respectively. Disease activity was the most powerful predictor of both single-dimensioned and multi-dimensioned fatigue. It was also found that the contribution of depression on fatigue was 12%. In conclusion, it was observed that half of the patients had severe fatigue, and multi-dimensional assessment was provided to understand specific aspects of fatigue better. Even though disease activity had a considerable effect on fatigue, the effects of psychogenic factors, especially depression, should be taken into consideration in the management of AS.