Background This study aims to investigate the correlation between the rising preterm birth rate (PBR) in Greece from 1991 to 2022 and the incidence of multiple births. Methodology Official data on live births in Greece from 1991 to 2022 were sourced from the Hellenic Statistical Authority. The PBR, defined as the number of live births occurring at <37 gestational weeks, and the multiple birth rate (MBR), representing live births from multifetal gestations, were calculated per 100 total live births. The relationship between the PBR and the MBR was evaluated using the non-parametric Spearman's rank correlation coefficient (rho). This association was confirmed through linear regression models, with MBR as the independent variable and PBR as the dependent variable, calculating the beta coefficient (β) and the coefficient of determination (R-squared). Results A very strong direct positive correlation was identified between PBR and MBR throughout the study period, with a Spearman's rho of 0.950 (p < 0.001). This conclusion was further supported by the linear regression model, which yielded a β coefficient of 3.32 (95% confidence interval = 2.78 to 3.86, p < 0.001). The R-squared was 0.838, indicating that the change in MBR explained 83.8% of the rise in PBR. The strongest correlations were observed for moderate PBR (32-33 weeks) with a rho of 0.962 (p < 0.001) and late PBR (34-36 weeks) with a rho of 0.940 (p < 0.001). During the period of a steep increase in prematurity rates in the country (1991-2011), an almost perfect correlation between PBR and MBR (rho = 0.987, p < 0.001) was noted. However, in recent years (2011-2022), characterized by a marginal increase in PBR, this association diminished, with a rho of 0.655 (p = 0.021). Conclusions This analysis revealed a strong positive correlation between the PBR and MBR in Greece from 1991 to 2022, underscoring the significant impact of multiple pregnancies on the substantial increase in preterm births within the Greek population.