The global molecular epidemiology of Mycoplasma pneumoniae (MP) and its associations with macrolide resistance and disease severity remain unclear. Studies reporting MP genotypes distribution by P1 typing, multiple locus variable number tandem repeat analysis (MLVA), or multilocus sequence typing analysis (MLST) among MP-infected patients were included. Data quality was assessed using the Joanna Briggs Institute tool and the Newcastle-Ottawa scale. Random-effects models were used to calculate pooled proportions of each MP genotype, with subgroup analyses by geographic region, age group, sex, time period, specimen type, and test assay. The proportions of macrolide-resistant MP and severe MP pneumonia cases were also evaluated. A total of 116 studies met the criteria. Predominant genotypes were P1-1 by P1 typing and 4572 by MLVA in the Western Pacific region and European region, and ST3 by MLST in the Western Pacific region. The proportions of P1-1 and 4572 were higher in the Western Pacific region than in other regions, and in children than in adults, whereas P1-2 and 3562 were opposite. Genotype dominance cycled between P1-1 and P1-2, and between 4572 and 3662. Macrolide resistance rates were highest in P1-1, 4572, and ST3 genotypes. Based on the currently available data, no association was detected between P1 genotypes and disease severity, although the limited sample size restricted the statistical power of this analysis. This comprehensive analysis elucidates the global molecular epidemiology of MP, highlights its clinical implications, and underscores the need for ongoing molecular surveillance to guide management and control strategies.