Abstract Objective To identify long-term trajectories of physical function and health-related quality of life (HRQoL) among people with hip and/or knee osteoarthritis (HKOA) and the sociodemographic, lifestyle, and clinical factors associated with different trajectories. Methods Participants with HKOA from the EpiDoC study, a 10-year follow-up (2011–2021) population-based cohort, were considered. Sociodemographic, lifestyle, and clinical variables were collected at baseline in a structured interview and clinical appointment. Physical function and HRQoL were evaluated with the Health Assessment Questionnaire (HAQ) and EuroQoL, respectively, at baseline and the three follow-ups. Group-based trajectory modeling identified physical function and HRQoL trajectories. Multinomial logistic regression analyzed the associations between the covariates of interest and trajectory assignment (p < 0.05). Results We included 983 participants with HKOA. We identified three trajectories for each outcome: “consistently low disability” (32.0%), “slightly worsening moderate disability” (47.0%), and “consistently high disability” (21.0%) for physical function; “consistently high HRQoL” (18.3%), “consistently moderate HRQoL” (48.4%) and “consistently low HRQoL” (33.4%) for HRQoL. Age ≥ 75 years, female sex, multimorbidity, and high baseline clinical severity were associated with higher risk of assignment to poorer physical function and HRQoL trajectories. Participants with high education level and with regular physical activity had a lower risk of assignment to a poor trajectory. Unmanageable pain levels increased the risk of assignment to the “consistently moderate HRQoL” trajectory. Conclusion Although the trajectories of physical function and HRQoL remained stable over 10 years, approximately 70% of people with HKOA maintained moderate or low physical function and HRQoL over this period. Modifiable risk factors like physical activity, multimorbidity and clinical severity were associated with poorer physical function and HRQoL trajectories. These risk factors may be considered in tailored healthcare interventions.