PURPOSE. To investigate the burden of visual impairment and comorbid fatigue in terms of impact on daily life, by estimating societal costs (direct medical costs and indirect non–health care costs) accrued by these conditions. METHODS. This cost-of-illness study was performed from a societal perspective. Cross-sectional data of visually impaired adults and normally sighted adults were collected through structured telephone interviews and online surveys, respectively. Primary outcomes were fatigue severity (FAS), impact of fatigue on daily life (MFIS), and total societal costs. Cost differences between participants with and without vision loss, and between participants with and without fatigue, were examined by (adjusted) multivariate regression analyses, including bootstrapped confidence intervals. RESULTS. Severe fatigue (FAS ≥ 22) and high fatigue impact (MFIS ≥ 38) was present in 57% and 40% of participants with vision loss (n = 247), respectively, compared to 22% (adjusted odds ratio [OR] 4.6; 95% confidence interval [CI] [2.7, 7.6]) and 11% (adjusted OR 4.8; 95% CI [2.7, 8.7]) in those with normal sight (n = 233). A significant interaction was found between visual impairment and high fatigue impact for total societal costs (€449; 95% CI [33, 1017]). High fatigue impact was associated with significantly increased societal costs for participants with visual impairment (mean difference €461; 95% CI [126, 797]), but this effect was not observed for participants with normal sight (€12; 95% CI [ 527, 550]). CONCLUSIONS. Visual impairment is associated with an increased prevalence of high fatigue impact that largely determines the economic burden of visual impairment. The substantial costs of visual impairment and comorbid fatigue emphasize the need for patient-centered interventions aimed at decreasing its impact.