© 2016 by the American College of Sports Medicine. Purpose Both moderate-to-vigorous physical activity (MVPA) and sedentary behavior can be associated with adult adiposity. Much of the relevant evidence is from cross-sectional studies or from prospective studies with relevant exposure measures at a single time point before weight gain or incident obesity. This study examined whether changes in MVPA and television (TV) viewing time are associated with subsequent changes in waist circumference, using data from three separate observation points in a large population-based prospective study of Australian adults. Methods Data were obtained from the Australian Diabetes, Obesity, and Lifestyle study collected in 1999-2000 (baseline), 2004-2005 (wave 2), and 2011-2012 (wave 3). The study sample consisted of adults age 25 to 74 yr at baseline who also attended site measurement at three time points (n = 3261). Multilevel linear regression analysis examined associations of initial 5-yr changes in MVPA and TV viewing time (from baseline to wave 2) with 12-yr change in waist circumference (from baseline to wave 3), adjusting for well-known confounders. Results As categorical predictors, increases in MVPA significantly attenuated increases in waist circumference (P for trend <0.001). TV viewing time change was not significantly associated with changes in waist circumference (P for trend = 0.06). Combined categories of MVPA and TV viewing time changes were predictive of waist circumference increases; compared with those who increased MVPA and reduced TV viewing time, those who reduced MVPA and increased TV viewing time had a 2-cm greater increase in waist circumference (P = 0.001). Conclusion Decreasing MVPA emerged as a significant predictor of increases in waist circumference. Increasing TV viewing time was also influential, but its impact was much weaker than MVPA.