Importance: Short- and long-term functional impairment after pediatric injury may be more sensitive for measuring quality of care compared with mortality alone. The characteristics of injured children and adolescents who are at the highest risk for functional impairment are unknown. Objective: To evaluate categories of injuries associated with higher prevalence of impaired functional status at hospital discharge among children and adolescents and to estimate the number of those with injuries in these categories who received treatment at pediatric trauma centers. Design, Setting, and Participants: This prospective cohort study (Assessment of Functional Outcomes and Health-Related Quality of Life After Pediatric Trauma) included children and adolescents younger than 15 years who were hospitalized with at least 1 serious injury at 1 of 7 level 1 pediatric trauma centers from March 2018 to February 2020. Exposure: At least 1 serious injury (Abbreviated Injury Scale score, =3 [scores range from 1 to 6, with higher scores indicating more severe injury]) classified into 9 categories based on the body region injured and the presence of a severe traumatic brain injury (Glasgow Coma Scale score <9 or Glasgow Coma Scale motor score <5). Main Outcomes and Measures: New domain morbidity defined as a 2 points or more change in any of 6 domains (mental status, sensory, communication, motor function, feeding, and respiratory) measured using the Functional Status Scale (FSS) (scores range from 1 [normal] to 5 [very severe dysfunction] for each domain) in each injury category at hospital discharge. The estimated prevalence of impairment associated with each injury category was assessed in the population of seriously injured children and adolescents treated at participating sites. Results: This study included a sample of 427 injured children and adolescents (271 [63.5%] male; median age, 7.2 years [interquartile range, 2.5-11.7 years]), 74 (17.3%) of whom had new FSS domain morbidity at discharge. The proportion of new FSS domain morbidity was highest among those with multiple injured body regions and severe head injury (20 of 24 [83.3%]) and lowest among those with an isolated head injury of mild or moderate severity (1 of 84 [1.2%]). After adjusting for oversampling of specific injuries in the study sample, 749 of 5195 seriously injured children and adolescents (14.4%) were estimated to have functional impairment at hospital discharge. Children and adolescents with extremity injuries (302 of 749 [40.3%]) and those with severe traumatic brain injuries (258 of 749 [34.4%]) comprised the largest proportions of those estimated to have impairment at discharge. Conclusions and Relevance: In this cohort study, most injured children and adolescents returned to baseline functional status by hospital discharge. These findings suggest that functional status assessments can be limited to cohorts of injured children and adolescents at the highest risk for impairment..