Exposure to high-altitude conditions during flight or similar activities affects many aspects of visual function, which is critical not only for flight safety but for any altitude-related activity. We aimed to summarize the available literature pertaining to ocular changes during flight or equivalent short-term high-altitude exposure (e.g., hypobaric chamber, effortless ascent lasting ≤ 24 h) and to highlight future research priorities. Using the PubMed/MEDLINE and Web of Science/ISI Web of Knowledge databases with structured search syntax, we conducted a systematic review of the literature spanning a 40-year period (January 1, 1983, to October 10, 2023). Articles pertaining to ocular changes during flight or flight-equivalent exposure to altitude were retrieved. The reference lists of retrieved studies were also searched, and citations of these references were included in the results. Of 875 relevant PubMed and ISI publications, 122 qualified for inclusion and 20 more were retrieved from the reference lists of initially selected records, for a total of 142 articles. Reported anterior segment changes included deterioration in tear film stability and increased dry eye incidence, increased corneal thickness, discomfort and bubble formation in contact lens users, refraction changes in individuals with prior refractive surgery, decreased intraocular pressure, and alterations in pupillary reaction, contrast sensitivity, and visual fields. Photoreceptor-visual pathway changes included alterations in both photoreceptors and neuro-transduction, as evidenced in dark adaptation, macular recovery time, reduction in visual field sensitivity, and optic neuritis (likely an element of decompression sickness). Retinochoroidal changes included increases in retinal vessel caliber, retinal blood flow, and choroidal thickness; central serous chorioretinopathy; and retinal vascular events (non-arteritic ischemic optic neuropathy, high-altitude retinopathy, and retinal vein occlusion). The effect of short-term high-altitude exposure on the eye is, in itself, a difficult area to study. Although serious impairment of visual acuity appears to be rare, ocular changes, including tear film stability, contact lens wear, central corneal thickness, intraocular pressure, contrast sensitivity, stability of refractive surgeries, retinal vessels, visual fields, and macula recovery time, should be considered in civilian aviators. Our report provides guidance to climbers and lowlanders traveling to altitude if they have pre-existing ocular conditions or if they experience visual symptoms while at altitude. However, key outcomes have been contradictory and comprehensive studies are scarce, especially those pertaining to the choroid and retina. Such studies could not only deepen our understanding of high-altitude ocular pathophysiology, but could also offer valuable information and treatment possibilities for a constellation of other vision-threatening diseases.