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Background: Cognitive impairment is one of the most common, burdensome, and costly disorders in the elderly worldwide. The magnitude of the association between anemia and overall cognitive impairment (OCI) has not been established. Objective: We aimed to update and expand previous evidence of the association between anemia and the risk of OCI. Methods: We conducted an updated systematic review and meta-analysis. We searched electronic databases, including EMBASE, PubMed, and Web of Science for published observational studies and clinical trials between 1 January 1990 and 1 June 2020. We excluded articles that were in the form of a review, letter to editors, short reports, and studies with less than 50 participants. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. We estimated summary risk ratios (RRs) with random effects. Results: A total of 20 studies, involving 6558 OCI patients were included. Anemia was significantly associated with an increased risk of OCI (adjusted RR (aRR) 1.39 (95% CI, 1.25–1.55; p < 0.001)). In subgroup analysis, anemia was also associated with an increased risk of all-cause dementia (adjusted RR (aRR), 1.39 (95% CI, 1.23–1.56; p < 0.001)), Alzheimer’s disease [aRR, 1.59 (95% CI, 1.18–2.13; p = 0.002)], and mild cognitive impairment (aRR, 1.36 (95% CI, 1.04–1.78; p = 0.02)). Conclusion: This updated meta-analysis shows that patients with anemia appear to have a nearly 1.39-fold risk of developing OCI than those without anemia. The magnitude of this risk underscores the importance of improving anemia patients’ health outcomes, particularly in elderly patients.