Background Participation of adolescents and young adults (AYAs) in oncology clinical trials is important to ensure adequate opportunities for AYA patients to contribute to, and benefit from, advances in cancer treatment. Methods Accrual data for National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) cooperative group‐led treatment trials were examined to assess enrollment of newly diagnosed AYA patients (15–39 years) during the period 2004–2019, with particular interest in comparing enrollment before launch of the NCI National Clinical Trials Network (NCTN) to after. All phase 2, 2/3, and 3 trials activated during the period between January 1, 2004, and December 31, 2019, were identified (n = 1568) and reduced to a set of 304 that met predetermined criteria to focus on cooperative group‐led trials that involved therapy for newly diagnosed cancer and had age eligibility overlapping the AYA range. The proportion of AYA patients relative to total accrual, along with 95% bootstrapped CI was calculated for patients enrolled pre‐NCTN and post‐NCTN. Results AYA accrual comprised 9.5% (95% CI, 7.6–11.8) pre‐NCTN compared with 14.0% (95% CI, 9.9–18.3) post‐NCTN. The mean difference in proportions post‐NCTN compared with pre‐NCTN was 4.4% (0.7%–8.3%). Conclusions These results indicate an increase in AYA participation in trials conducted within the NCTN relative to the pre‐NCTN period. This suggests an awareness and utilization of NCTN trials for AYAs with cancer. Lay summary Five‐year relative survival for newly diagnosed adolescent and young adult (AYA) patients (15–39 years) with cancer is estimated at approximately 85% overall. However, outcomes tend to be worse for certain high‐risk AYA subsets, and AYAs remain challenged by multiple issues that could be addressed effectively through improved enrollment of AYAs onto clinical trials. This study assessed participation of AYA patients newly diagnosed with cancer in National Cancer Institute (NCI) Cancer Therapy Evaluation Program‐sponsored clinical trials before and after launch of the NCI National Clinical Trials Network. Trends in enrollment of adolescent and young adult (AYA) patients participating in National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)‐sponsored cancer treatment trials during the period 2004–2019 are examined. Comparing enrollment prior to the launch of the NCI National Clinical Trials Network in 2014 to that after, a proportionate increase in enrollment of AYA patients is observed.