Background: The aim of this systematic review and meta-analysis was to determine the wear sustained in the natural antagonist tooth in cases of full-coverage fixed-base prosthetic restorations or monolithic zirconia tooth-supported crowns, as well as to determine the wear in the restoration itself, both in the short- and medium-term and considering the factors that may influence wear. Material and methods: A systematic literature review and meta-analysis, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, of clinical studies that evaluated wear in antagonist teeth in relation to fixed-prosthesis monolithic zirconia crowns. A total of 5 databases were consulted in the literature search: Pubmed-Medline, Cochrane, Scopus, Embase and Web of Science (WOS). After eliminating duplicated articles and applying the inclusion criteria, eight articles were selected for the qualitative analysis and four for the quantitative analysis. Results: Mean maximum wear of the antagonist tooth in relation to monolithic zirconia crowns of magnitude 95.45 µm (CI at 95% 79.57–111.33) was observed. By using a meta-regression model (R² = 0.92) the significant effect of time in maximum wear rate (p < 0.001) was observed, estimated at 6.13 µm per month (CI at 95% 3.99–8.27). Furthermore, monolithic zirconia crowns are subject to a mean maximum wear of 58.47 µm (CI 95% 45.44–71.50). By using a meta-regression model (R² = 0.53) the significant effect of time in the maximum wear value was observed (p = 0.053), estimated at 3.40 µm per month (CI al 95% −0.05–6.85). Conclusions: Monolithic zirconia crowns lead to a progressive maximum wear of the antagonist tooth over time which is greater than the maximum wear sustained in the crown itself. It is not possible to establish an objective and quantitative objection in relation to natural enamel wear or metal–ceramic crowns.