The purpose of this cross-sectional study was to compare health-related quality of life (HRQoL) and depressive symptoms among peri-postmenopausal women with polycystic ovary syndrome (PCOS) aged ≥43 years relative to premenopausal women with PCOS aged 18–42 years. An online survey link comprising questionnaires about demographics, HRQoL, and depressive symptoms was posted onto two PCOS-specific Facebook groups. Respondents (n = 1,042) were separated into two age cohorts: women with PCOS aged 18–42 years (n = 935) and women with PCOS aged ≥43 years (n = 107). Data from the online survey were analyzed using descriptive statistics, Pearson correlations, and multiple regression via SAS. Results were interpreted through the lens of life course theory. All demographic variables, except for the number of comorbidities, significantly differed between groups. HRQoL among older women with PCOS was significantly better as compared to those aged 18–42 years. Results indicated significant positive linear associations between the HRQoL psychosocial/emotional subscale and other HRQoL subscales and a significant negative association with age. The fertility and sexual function HRQoL subscales were not significantly associated with the psychosocial/emotional subscale among women aged ≥43 years. Women in both groups had moderate depressive symptoms. Study findings demonstrate the need to tailor PCOS management to women’s life stage. This knowledge can inform future research about peri-postmenopausal women with PCOS and age-appropriate and patient-centered healthcare, including requisite clinical screenings (e.g., depressive symptoms) and lifestyle counseling across the lifespan.