Objective: To investigate the prevalence of fatigue and identify its associated influencing factors in patients with inflammatory bowel disease (IBD), thereby providing an evidence base for targeted clinical interventions. Methods: A cross-sectional survey design was adopted. A total of 204 patients with confirmed IBD diagnoses were consecutively enrolled from the gastroenterology outpatient clinics and inpatient wards of a tertiary-level hospital in Shiyan, Hubei Province, China, between June 2023 and June 2024. Fatigue was assessed using the IBD-Fatigue (IBD-F) scale. Sociodemographic characteristics, disease-related parameters, inflammatory biomarkers, and psychological status were simultaneously collected. Univariable analyses and multivariable logistic regression were performed to identify independent determinants of fatigue. Results: Among the 204 enrolled IBD patients, 142 (69.61%) had fatigue (IBD-F ≥ 13). Univariable analyses revealed that sex, disease activity status, anemia, C-reactive protein (CRP) level, serum albumin level, sleep quality, anxiety, and depression were significantly associated with fatigue occurrence (all p < 0.05). Multivariable logistic regression identified active disease phase (OR = 3.12, 95% CI: 1.54–6.31, p = 0.002), comorbid anemia (OR = 2.87, 95% CI: 1.42–5.80, p = 0.004), elevated CRP (OR = 2.43, 95% CI: 1.21–4.88, p = 0.013), poor sleep quality (OR = 2.19, 95% CI: 1.10–4.36, P = 0.026), and comorbid depression (OR = 3.56, 95% CI: 1.76–7.19, p = 0.001) as independent risk factors for fatigue; serum albumin ≥ 35 g/L was identified as a protective factor (OR = 0.48, 95% CI: 0.24–0.96, p = 0.037). Fatigue was significantly and negatively correlated with health-related quality of life (r = −0.61, p < 0.001). Conclusion: The prevalence of fatigue in IBD patients is as high as 69.61%, and it is independently associated with disease activity, elevated inflammatory markers, anemia, sleep disturbance, and depression, significantly impairing patients' quality of life. Routine fatigue screening and comprehensive multidimensional management strategies should be integrated into standard IBD care.