Purpose: The aim was to compare fatigue levels between patients with visual impairment and controls with normal sight and to examine the association between fatigue and vision loss severity. Methods: A systematic literature search was performed using databases of PubMed, Embase, PsycINFO and Cochrane to identify observational studies with outcomes related to fatigue (e.g. vitality subscale of the Short-Form 36, Fatigue Assessment Scale). A meta-analysis was performed using standardised mean differences (SMDs) and odds ratios (OR) to quantitatively summarise the association between visual impairment and fatigue. Sources of heterogeneity were explored by subgroup and sensitivity analyses. Study quality was assessed with the Newcastle-Ottawa scale. Results: After reviewing 4477 studies, 22 studies with a total of 40 004 participants were included, of which 18 contributed to meta-analysis. Among these, eight were assessed as moderate quality studies and 10 as high quality studies. Pooled analysis involving 2500 patients and 8395 controls showed higher fatigue severity levels (S.M.D. = −0.36, 95% CI −0.50 to −0.22, 14 studies) among visually impaired patients compared to normally sighted controls. This effect size was small and persisted in sensitivity analyses that involved study quality, fatigue assessment tools and visual acuity data. Furthermore, pooled analysis of four studies including 2615 patients and 5438 controls showed a significant association between visual impairment and fatigue (OR = 2.61, 95% CI 1.69 to 4.04). Secondary meta-analysis of four studies showed no significant difference in fatigue severity (S.M.D. = 0.01, 95% CI −0.37 to 0.39) between patients with moderate visual impairment and patients with severe visual impairment or blindness. Conclusions: Current moderate to high quality evidence suggest that patients with visual impairment experience more severe fatigue symptoms than persons with normal sight. However, a limited number of available studies indicates that fatigue is not associated with severity of vision loss. Future studies are required to determine which factors and underlying mechanisms may explain the association between visual impairment and fatigue. Discussing fatigue at an early stage and developing intervention options for vision-related fatigue should be considered within the field of low vision rehabilitation.