The mechanisms contributing to age-related deterioration of the female reproductive system are complex, but aberrant protein homeostasis is a major contributor. We elucidated the exceptionally stable proteins, structures, and macromolecules that persist in mammalian ovaries and gametes across the reproductive lifespan. Ovaries exhibit localized structural and cell-type specific enrichment of stable macromolecules in both the follicular and extrafollicular environments. Moreover, both ovaries and oocytes harbor a panel of exceptionally long-lived proteins, including cytoskeletal components, mitochondrial, and oocyte-derived proteins. The exceptional persistence of these long-lived molecules might play a critical role in both lifelong maintenance and age-dependent deterioration of reproductive tissues.