Objective: To examine whether body mass index (BMI), menopausal status, and hormone therapy (HT) use modify the association between physical activity (PA) patterns throughout middle age and the incidence and prevalence of joint symptoms in women in later middle age. Methods: Data were from 6,661 participants (born 1946–1951) in the Australian Longitudinal Study on Women's Health. Surveys, with questions on joint pain and stiffness, PA, height and weight, menopausal symptoms, and HT use, were completed every 3 years from 1998 to 2010. PA patterns were defined as none or low, low or meeting guidelines, fluctuating, or meeting guidelines at all times (reference pattern). Logistic regression was used to examine the association between PA patterns and prevalent (in 2010) and cumulative incident (1998–2010) joint symptoms and effect modification by patterns in BMI, menopausal status, and HT. Results: The groups representing fluctuating PA (odds ratio [OR] 1.34 [99% confidence interval (99% CI) 1.04–1.72]) and no or low PA (OR 1.60 [99% CI 1.08–2.35]) had higher odds of incident joint symptoms than those described as meeting guidelines at all times. Stratification by BMI showed that this association was statistically significant in the obese group only. No evidence for effect modification by menopausal status or HT use was found. The findings were similar for prevalent joint symptoms. Conclusion: Maintaining at least low levels of PA throughout middle age was associated with a lower prevalence and incidence of joint symptoms later in life. This apparent protective effect of PA on joint symptoms was stronger in obese women than in under- or normal-weight women, and not related to menopause or HT status.