Background: Despite promotion of physical activity guidelines, less than one third of U.S. adults are sufficiently active and an even larger number of older adults fail to meet guidelines. To address this major public health issue, it is essential to broadly consider determinants of physical activity. Aims: This study explores how physical activity behavior is affected by the experience of major life events and considers the stress experienced due to these events across the life course. Method: Nationally representative panel data from the Americans' Changing Lives survey (1986-2012) was used to analyze a growth model with age-based trajectories to examine the relationship between major life events and physical activity overall and separately by gender and race. Results: In the overall sample, retiring was associated with greater physical activity at baseline. As respondents aged, entering into retirement was associated with decreased physical activity, while a parent or friend dying was associated with greater physical activity. Differences by gender and race were also seen over time. Conclusions: Results show that when considering physical activity trajectories, experiencing these major life events is not always detrimental, and in some cases may be beneficial. Considering these impacts is important in planning effective health promotion interventions to increase and promote maintenance of physical activity, while paying attention to specific differences by gender and race.