Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SAR2-COV-2) and was first identified in Wuhan, China, in December of 2019, but quickly spread to the rest of the world, causing a pandemic. While some studies have found no link between smoking status and severe COVID-19, others demonstrated a significant one. The present study aimed to determine the relationship between smoking and clinical COVID-19 severity via a systematic meta-analysis approach. Methods: We searched the Google Scholar, PubMed, Scopus, Web of Science, and Embase databases to identify clinical studies suitable for inclusion in this meta-analysis. Studies reporting smoking status and comparing nonsevere and severe patients were included. Nonsevere cases were described as mild, common type, nonintensive care unit (ICU) treatment, survivors, and severe cases as critical, need for ICU, refractory, and nonsurvivors. Results: A total of 16 articles detailing 11322 COVID-19 patients were included. Our meta-analysis revealed a relationship between a history of smoking and severe COVID-19 cases (OR = 2.17; 95% CI: 1.37-3.46; P < .001). Additionally, we found an association between the current smoking status and severe COVID-19 (OR = 1.51; 95% CI: 1.12-2.05; P < .008). In 10.7% (978/9067) of nonsmokers, COVID-19 was severe, while in active smokers, severe COVID-19 occurred in 21.2% (65/305) of cases. Conclusion: Active smoking and a history of smoking are clearly associated with severe COVID-19. The SARS-COV-2 epidemic should serve as an impetus for patients and those at risk to maintain good health practices and discontinue smoking. The trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) CRD42020180173.