Understanding how chronic conditions such as knee osteoarthritis (OA) and chronic obstructive pulmonary disease (COPD) influence long-term physical activity (PA) is essential for developing condition-specific rehabilitation strategies. This study aimed to examine whether baseline diagnoses of knee OA and COPD are independently associated with the trajectories of PA decline over five years in U.S. adults, informed by the disablement process model. We analyzed data from 855 adults aged ≥45 years enrolled in the Osteoarthritis Initiative (OAI). The participants were categorized into three baseline groups, control ( = 122), knee OA ( = 646), and COPD ( = 87), based on self-reports and prior clinical assessments. PA was measured annually for five years using the Physical Activity Scale for the Elderly (PASE). General linear mixed models assessed changes in PA over time, adjusting for demographic, behavioral, and clinical covariates. Compared to the controls, participants with knee OA had a significant decline in PA over time (β = -6.62; 95% CI: -15.4 to -2.19; = 0.014). Those with COPD experienced an even greater decline compared to the knee OA group (β = -11.2; 95% CI: -21.7 to -0.67; = 0.037). These associations persisted after adjusting for age, sex, body mass index, comorbidities, and smoking. Baseline knee OA and COPD were independently associated with long-term reductions in PA. These findings underscore the importance of early, tailored rehabilitation strategies, particularly pulmonary rehabilitation, in preserving functional independence among older adults with chronic conditions.