Age-related macular degeneration (AMD) is the most prevalent cause of irreversible vision loss in industrialized countries. Several studies have investigated systemic interleukin-6 (IL-6) levels of patients with AMD. In this study, we systemically reviewed the literature to provide an overview of the field and used meta-analyses to provide a summary estimate of the standardized mean difference (SMD) of systemic IL-6 between patients with AMD and control individuals. We searched the literature databases PubMed/MEDLINE, Embase, Web of Science and the Cochrane Central on 1 June 2019 for relevant studies on humans. Two authors independently extracted data and evaluated risk of bias. We identified 19 studies for the qualitative review with a total of more than 3586 individuals (1865 controls and 1721 with AMD). We found an overall random-effects SMD in systemic IL-6 levels 0.63 (95% CI: 0.28 to 0.99, p = 0.0005) corresponding to a medium effect size. In a subgroup analysis, we found that early AMD was not strongly associated with elevated IL-6 levels (0.12, 95% CI: -0.01 to 0.24, p = 0.06), which was in contrast to the significantly elevated IL-6 levels in patients with geographic atrophy (1.21, 95% CI: 0.41 to 2.01, p = 0.003) and patients with neovascular AMD (0.99, 95% CI: 0.34 to 1.63, p = 0.003). Our results show that the evidence today suggests an increased systemic IL-6 in patients with AMD, but that this may be a phenomenon more closely related to the late subtypes of AMD.