Aim This study investigated changes in small-world topology and brain functional connectivity in patients with optic neuritis (ON) by resting-state functional magnetic resonance imaging (rs-fMRI) and based on graph theory. Methods A total of 21 patients with ON (8 males and 13 females) and 21 matched healthy control subjects (8 males and 13 females) were enrolled and underwent rs-fMRI. Data were preprocessed and the brain was divided into 116 regions of interest. Small-world network parameters and area under the integral curve (AUC) were calculated from pairwise brain interval correlation coefficients. Differences in brain network parameter AUCs between the 2 groups were evaluated with the independent sample t-test, and changes in brain connection strength between ON patients and control subjects were assessed by network-based statistical analysis. Results In the sparsity range from 0.08 to 0.48, both groups exhibited small-world attributes. Compared to the control group, global network efficiency, normalized clustering coefficient, and small-world value were higher whereas the clustering coefficient value was lower in ON patients. There were no differences in characteristic path length, local network efficiency, and normalized characteristic path length between groups. In addition, ON patients had lower brain functional connectivity strength among the rolandic operculum, medial superior frontal gyrus, insula, median cingulate and paracingulate gyri, amygdala, superior parietal gyrus, inferior parietal gyrus, supramarginal gyrus, angular gyrus, lenticular nucleus, pallidum, superior temporal gyrus, and cerebellum compared to the control group (P < 0.05). Conclusion Patients with ON show typical “small world” topology that differed from that detected in HC brain networks. The brain network in ON has a small-world attribute but shows reduced and abnormal connectivity compared to normal subjects and likely causes symptoms of cognitive impairment.