We describe 10-year changes in accelerometer-determined physical activity (PA) and sedentary time in a midlife cohort of the Coronary Artery Risk Development in Young Adults Study, within and by race and sex groups. Participants (n = 962) wore the accelerometer with valid wear (≥4 of 7 days, ≥10 hours per day) at baseline (2005-2006; ages 38-50 years) and 10-year follow-up (2015-2016; ages 48-60 years). Data were calibrated to account for accelerometer model differences. Participants (mean age = 45.0 (standard deviation, 3.5) years at baseline) had reduced accelerometer counts overall (mean = -65.5 (standard error (SE), 10.2) counts per minute/day), and within race and sex groups (all P < 0.001). Sedentary time increased overall (mean = 37.9 (SE, 3.7) minutes/day) and within race and sex groups, whereas light-intensity PA (mean = -30.6 (SE, 2.7) minutes/day) and moderate- to vigorous-intensity PA (mean = -7.5 (SE, 0.8) minutes/day) declined overall and within race and sex groups (all P < 0.001). Significant differences in 10-year change estimates were noted by race and sex groups for accelerometer counts, sedentary time, and moderate- to vigorous-intensity PA bouts; black men had the greatest reductions in PA compared with other groups. PA declines during midlife were characterized by reductions in light-intensity PA with increases in sedentary time, which may have important health consequences. Targeted efforts are needed to preserve PA, regardless of intensity level, across midlife.