Multiple sclerosis (MS) is associated with different ocular disorders. This study aimed to investigate the retinal microvascular changes detected by optical coherence tomography angiography (OCTA) in eyes with MS with or without a history of optic neuritis (ON). A comprehensive literature search was conducted in the Web of Science, Embase, PubMed, and Cochrane Library databases on September 26, 2021 for articles focused on OCTA manifestations in the eyes of MS patients compared with healthy controls. RevMan Manager (v.5.4) and Stata (v.14.1) were used to analyze the main differences and publication risks. Weighted mean differences and 95% confidence intervals were calculated for continuous estimates. This study also included subgroup analysis between three groups: eyes with multiple sclerosis and with optic neuritis (MSON); eyes with multiple sclerosis and without optic neuritis (MSNON); and healthy controls. Thirteen studies with a total of 1803 eyes were identified, including 957 eyes with MS and 846 eyes of healthy controls. The vessel density of the MS eyes decreased significantly in most areas of the radial peripapillary capillary. A marked reduction in the macular superficial capillary plexus of MS eyes regardless of ON history was also confirmed. The results suggest that MS patients demonstrated significant retinal microvasculature impairment regardless of ON history, compared to healthy controls. Retinal vessel density attenuation detected by OCTA may serve as a reliable early marker of MS.