Physical activity (PA) is a key contributor in long-term weight management but there remains limited research on the association between weekly PA patterns and weight change. The purpose of the present study was to examine the prospective association between weekly PA patterns and weight change in generally healthy young adults. Anthropometric measurements, including dual X-ray absorptiometry, were obtained every 3 months over a period of one year in 338 adults (53% male). At each measurement time, participants wore a multisensor device for a minimum of 10 days to determine total daily energy expenditure and time spent sleeping, sedentary, in light PA (LPA), in moderate PA (MPA), and in vigorous PA (VPA). PA did not differ between weekdays and the weekend at baseline. Twenty-four-hour sleep time, however, was significantly longer during weekends compared to weekdays, which was associated with less time spent sedentary. Weight loss was associated with a significant increase in LPA at the expense of sedentary time during the weekend but not during weekdays. Regression analyses further revealed an inverse association between change in VPA during the weekend and body composition at 12-month follow-up. Taken together, these results suggest that weekend PA plays an important role in long-term weight management.