Technical Abstract: Physical activity can enhance quality of life for cancer survivors. However, few longitudinal studies have examined whether physical activity has a sustained effect on improvements in quality of life. The present study aims to examine the relationships between physical activity and quality of life over 2 years after a colorectal cancer diagnosis. Data were collected within the Colorectal Cancer and Quality of Life Study, in which 1,966 people diagnosed with colorectal cancer were recruited through the Queensland Cancer Registry. Participants completed telephone interviews at approximately 6, 12, and 24 months after diagnosis. Generalized linear mixed models were used to estimate the overall, interindividual, and intraindividual level independent effects of participation in physical activity on quality of life. There was an overall independent association between physical activity and quality of life. At a given time point, participants achieving at least 150 minutes of physical activity per week had an 18% higher quality of life score than those who reported no physical activity. Significant associations were also present at the interindividual level (differences between participants) and intraindividual level (within participant changes). These findings suggest that the positive association between physical activity and quality of life is consistent over time. Encouraging colorectal cancer survivors to be physically active may be a helpful strategy for enhancing quality of life.