Objective Metabolic syndrome (MetS) is a clustering of at least three of the following four medical conditions: obesity, hypertension, dyslipidemia, and hyperglycemia. We aimed to discover the relationships between these diseases and osteoarthritis (OA) of the knee. Methods We searched four databases (EMBASE, PubMed, Cochrane Library, and MEDLINE), as well as articles on websites and conference materials. Study effect estimates and their 95% confidence intervals (CIs) were extracted and calculated. Sensitivity analyses were undertaken to determine inter-study heterogeneity. Finally, we tested for publication bias to determine whether the outcome of the meta-analysis was robust. Results A total of 1609 articles were identified, 40 of which were included. In radiological studies, the relationships with OA were increased for people with the following diseases: metabolic syndrome (OR 1.418, 95% CI 1.162 to 1.730), hypertension (OR 1.701, 95% CI 1.411 to 2.052), and hyperglycemia (OR 1.225, 95% CI 1.054 to 1.424). In symptomatic studies, the outcomes were similar in metabolic syndrome (OR 1.174, 95% CI 1.034 to 1.332) and hypertension (OR 1.324, 95% CI 1.186 to 1.478) studies, while there were no associations in hyperglycemia (OR 0.975, 95% CI 0.860 to 1.106) studies. There was no correlation between dyslipidemia and OA, whether in radiological studies (OR 1.216, 95% CI 0.968 to 1.529) or symptomatic studies (OR 1.050, 95% CI 0.961 to 1.146). Conclusions In both studies, metabolic syndrome and hypertension were positively associated with knee OA, and dyslipidemia showed no correlations. Hyperglycemia was associated with OA in radiological studies, while results were reversed in symptomatic studies.