BACKGROUND: Physical activity (PA) and sedentary behavior (SB) are not stable conditions but change over time and among individuals, and both could have deleterious effects on health-related outcomes among older adults. This study aimed to identify the longitudinal trajectories of PA and SB and estimate their association with quality of life, disability, and all-cause mortality in a national sample of older Mexican adults. METHODS: Data comes from three waves of the WHO Study on global AGEing and adult health (SAGE) in Mexico (2009, 2014, 2017). In total, 3209 older adults ages 50 and above were included. PA and SB were determined by using the Global Physical Activity Questionnaire (GPAQ). Disability was measured using the WHO Disability Assessment Schedule (WHODAS 2.0), quality of life using the WHOQOL (WHO Quality of Life) instrument, and all-cause mortality using a verbal autopsy. We used growth mixture modeling (GMM) to investigate the longitudinal trajectories of PA and SB. Three-level linear mixed effect models were used to estimate the associations of PA and SB with quality of life and disability and the Cox model for the association with all-cause mortality. RESULTS: Three longitudinal trajectories of PA and SB were found: low-PA-decreasers, moderate-PA-decreasers, and high-PA-decreasers for PA; and low-maintainers, steep-decreasers, and steep-increasers for SB. Decreased quality of life, increased disability, and all-cause mortality were all consistently associated with worse PA and SB trajectories. CONCLUSIONS: Our results highlight the need for health policies and prevention strategies that promote PA and limit SB in middle-aged adults. Further studies should consider these activities/behaviors as exposures that vary throughout life and work to identify vulnerable groups of older adults for whom physical activation interventions and programs would be most impactful.