Purpose: To analyze functional connectivity (FC) of the visual cortex using resting-state functional MRI in human primary open-angle glaucoma (POAG) patients. Materials and Methods: Twenty-two patients with known POAG and 22 age-matched controls were included in this IRB-approved study. Subjects were evaluated by 3 T MR using resting-state blood oxygenation level dependent and three-dimensional brain volume imaging (3D-BRAVO) MRI. Data processing was performed with standard software. FC maps were generated from Brodmann areas (BA) 17/18/19/7 in a voxel-wise fashion. Region of interest analysis was used to specifically examine FC among each pair of BA17/18/19/7. Results: Voxel-wise analyses demonstrated decreased FC in the POAG group between the primary visual cortex (BA17) and the right inferior temporal, left fusiform, left middle occipital, right superior occipital, left postcentral, right precentral gyri, and anterior lobe of the left cerebellum. Increased FC was found between BA17 and the left cerebellum, right middle cerebellar peduncle, right middle frontal gyrus, and extra-nuclear gyrus (P < 0.05). In terms of the higher visual cortices (BA18/19), positive FC was disappeared with the cerebellar vermis, right middle temporal, and right superior temporal gyri (P < 0.05). Negative FC was disappeared between BA18/19 and the right insular gyrus (P < 0.05). Region of interest analysis demonstrated no statistically significant differences in FC between the POAG patients relative to the controls (P > 0.05). Conclusion: Changes in FC of the visual cortex are found in patients with POAG. These include alterations in connectivity between the visual cortex and associative visual areas along with disrupted connectivity between the primary and higher visual areas. Hum Brain Mapp 34:2455–2463, 2013. © 2012 Wiley Periodicals, Inc.