Importance: Faster structural changes may be associated with worse vision-related quality of life in patients with glaucoma. Objectives: To evaluate the association between the rate of ganglion cell complex thinning and the Vision Function Questionnaire in glaucoma. Design, Setting, and Participants: This retrospective analysis of a longitudinal cohort was designed in October 2021. Patients were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Two hundred thirty-six eyes of 118 patients with diagnosed or suspected glaucoma were followed up with imaging for a mean of 4.1 years from September 2014 to March 2020. Main Outcomes and Measures: The Vision Function Questionnaire was evaluated using the 25-item National Eye Institute Visual Function at the last follow-up visit. Ganglion cell complex thickness was derived from macular optical coherence tomography scans and averaged within 3 circular areas (3.4°, 5.6°, and 6.8° from the fovea) and superior and inferior hemiregions. Linear mixed-effects models were used to investigate the association between the rate of ganglion cell complex thinning and Rasch-calibrated Vision Function Questionnaire score. Results: The mean (SD) age was 73.2 (8.7) years, 65 participants (55.1%) were female, and 53 participants (44.9%) were African American. Race was self-reported by the participants. Mean composite Rasch-calibrated National Eye Institute Visual Function Questionnaire score was 50.3 (95% CI, 45.9-54.6). A faster annual rate of global ganglion cell complex thinning in the better eye was associated with a higher disability reflected by the composite National Eye Institute Visual Function Questionnaire score (-15.0 [95% CI, -28.4 to -1.7] per 1 μm faster; P =.03). When stratified by degrees from the fovea, the 5.6° and 6.8° areas were associated with the composite National Eye Institute Visual Function Questionnaire Rasch-calibrated score (-14.5 [95% CI, -27.0 to -2.0] per 1 μm faster; R2= 0.201; P =.03; and -23.7 [95% CI, -45.5 to -1.9] per 1 μm faster; R2= 0.196; P =.02, respectively), and -8.0 (95% CI, -16.8 to 0.8) per 1 μm faster for the 3.4° area (R2= 0.184; P =.07) after adjusting for confounding factors. Conclusions and Relevance: These findings suggest that faster and sectoral central location of ganglion cell complex thinning provides useful information in determining the risk of vision-related quality of life in glaucoma. Monitoring macular structure may be useful for determining the risk of functional impairment in glaucoma..