To evaluate the effectiveness of a multilevel intervention using national partnerships on human papillomavirus (HPV) vaccination rates. The American Cancer Society's Vaccinate Adolescents against Cancer program is a multilevel intervention focusing on systems and providers. The 2017 cohort introduced national partnerships to deliver intervention elements and Maintenance of Certification and continuing medical education credits for physicians. Eleven federally qualified health center (FQHC) systems completed interventions in 2017. Interventions included provider training and ≥1 other evidence-based systems improvement. We compared adolescent vaccination rates in the preintervention period (2016) and intervention period (2017) among adolescents who turned 13 during the calendar year. Intervention effectiveness was assessed using repeated measures paired t tests and Cohen's d effect size for vaccination rate change. All FQHC systems implemented provider training plus an average of 2.3 additional systems improvements. Series initiation increased by an average of 23.6 percentage points (47.2%-70.8%). HPV completion rates increased by an average of 22.7 percentage points (24.6%-46.3%). Meningococcal and Tdap vaccination rates increased by 23.3 and 25.9 percentage points respectively (47.9%-71.2% and 48.8%-74.7%). All changes were statistically significant (all P < .05) and indicated large effect sizes (Cohen's d3 1.15). Among clinicians completing postintervention surveys, 90% reported making changes to their health care system or direct patient care based on what they had learned. Multilevel interventions focusing on provider training and systems changes can substantially improve on-time adolescent vaccination coverage and can be successfully performed using national partnerships and a train-the-trainer model.