ObjectiveDetermine trends and survival implications of adjuvant systemic therapy use for lower risk head and neck cancer.Study DesignRetrospective cohort study.SettingUS National Cancer Database, 2010 to 2019.MethodsPatients with mucosal head and neck squamous cell carcinoma treated with surgery and postoperative radiation therapy were identified. Adjuvant systemic therapy trends in those with and without extranodal extension or positive margins were assessed as annual percent change by JoinPoint analysis. Factors associated with adjuvant systemic therapy and overall survival were assessed with multivariable models and cox proportional hazard models, respectively.ResultsFrom 2010 to 2019, approximately one‐third of head and neck cancer patients without extranodal extension or positive margins received adjuvant systemic therapy. This rate decreased throughout the study period, with the highest annual percent change from 2016 to 2019 (12.21%; 95% confidence interval: 3.73%‐19.95%). Younger age, male sex, Hispanic ethnicity, community program setting, advanced stage, and lymphovascular invasion increased the odds a patient would receive adjuvant systemic therapy. Adjuvant systemic therapy was associated with inferior overall survival when used in those without extranodal extension or positive margins after controlling for covariates.ConclusionThough decreasing, adjuvant systemic therapy use is still common in the absence of extranodal extension and positive margins, and a variety of patient, provider, and oncologic factors may influence its use. The inferior overall survival after adjuvant systemic therapy in the absence of high‐risk features suggests any oncologic benefit may not outweigh the costs and morbidity of the therapy.