This study examined the effects of a 12-week Comprehensive School Physical Activity Program (CSPAP) on gross motor skill development in children from low-income families. Participants were 1,460 school-aged children (mean age = 8.4 ± 1.8 years; 730 girls, 730 boys) recruited from three schools receiving U.S. governmental financial assistance. Students were recruited from grades K−6. CSPAP was implemented over one semester during the 2014−2015 school year. Select gross motor skill items were assessed during each student’s physical education class at baseline and at a 12-week follow-up using the Test for Gross Motor Development-2nd Edition (TGMD-2). Each student’s TGMD-2 score was converted to a percentage of the total possible score. A 7 × 2 × 2 analysis of variance test with repeated measures was employed to examine the effects of age, sex, and time on TGMD-2 percent scores, adjusting for clustering within the data structure. There were greater TGMD-2 percent scores at follow-up compared with baseline (82.4% vs. 72.6%, mean difference = 9.8%, p < .001, Cohen’s d = 0.67), and greater improvements were seen in younger children compared with older children (mean difference of change = 4.0%−7.5%, p < .01, Cohen’s d = 0.30−0.55).