Background: Ultra-processed food (UPF) intake has been increasingly recognized as an important dietary target for obesity prevention among youths, yet evidence on UPF intake and weight gain from longitudinal studies is limited. We aimed to evaluate the association between UPF intake and weight patterns in a large cohort of US children and adolescents. Methods: Study participants included children and adolescents (aged 7-17 years) enrolled in the Growing Up Today Studies 1 (GUTS1) and 2 (GUTS2) who completed baseline and had at least one additional assessment on diet and weight/height during follow-up (GUTS1 1996-2001: N=15,023; GUTS2 2004-2011: N=9,156). UPF was categorized based on the NOVA classification and intake was evaluated as percent energy (%E) from UPF over total daily calories. Change in self-reported weight status was assessed using change in body mass index (BMI), a more sensitive measure of adiposity change than BMI z-score in youth. Changes in BMI in association with UPF intake over 2, 4-5, and 7 years were evaluated using multivariate repeated-measure linear mixed models. Association between UPF intake and obesity risk was assessed in secondary analyses. Results: At baseline, the %E from UPF in children and adolescents was 49.9% and 49.5% in GUST1 and GUST2, respectively; the mean BMI was 18.7 kg/m2 and 19.8 kg/m2 in GUST1 and GUST2, respectively. A higher %E from UPF was associated with higher levels of total calorie intake, lower diet quality, longer sedentary time, and lower levels of family income and parental education. After multivariate adjustments for sociodemographic and lifestyle risk factors, each 10% increment in %E from UPF was associated with a 0.08 95% CI: 0.03-0.14 kg/m2 increase over 5 years in GUTS1 participants, and a 0.13 0.02-0.24 kg/m2 increase over 7 years in GUTS2 participants. No association was found between UPF intake and obesity risk. Conclusions: A higher UPF consumption was associated with greater increases in BMI in large prospective cohorts of children and adolescents in the US. Findings call for public health efforts to limit UPF consumption in youth to prevent excessive weight gain.