This study challenges historical paradigms using a large-scale integrated bioarchaeological approach, focusing on the female experience over the last 2,000 years in Milan, Italy. Specifically, 492 skeletons from the osteological collection of Milan were used to elucidate female survivorship and mortality by integrating bioarchaeological and paleopathological data, paleoepidemiological analyses, and historical contextualization. Findings revealed changes in female longevity, with a notable increase from Roman to contemporary eras, albeit plateauing in the Middle Ages/modern period. Significant sex-specific differences in mortality risk and survivorship were observed: females had higher mortality risk and lower survivorship in the Roman (first-fifth century AD) and Modern (16th-18th century AD) eras, but this trend reversed in the contemporary period (19th-20th century AD). Cultural and social factors negatively impacted female mortality in Roman and modern Milan, while others buffered it during the Middle Ages (sixth-15th century AD). This study underscored the importance of bioarchaeological inquiries in reconstructing the past, providing answers that may challenge historical assumptions and shedding light on how the interplay of cultural, social, and biological factors shaped the female experience across millennia.