Background Human papillomavirus (HPV)–mediated oropharyngeal cancer (OPC) is associated with dramatically improved survival in comparison with HPV‐negative OPC and can be successfully treated with surgical and nonsurgical approaches. National treatment trends for OPC were investigated with the National Cancer Data Base (NCDB). Methods The NCDB was reviewed for primary HPV‐mediated OPC in 2010‐2014. Multivariable regression was used to identify predictors of both nonsurgical therapy and receipt of adjuvant chemoradiation (CRT). Results There were 13,363 patients identified with a median age at diagnosis of 58 years. The incidence of triple‐modality treatment (surgery with adjuvant chemotherapy) decreased from 23.7% in 2010 to 16.9% in 2014 (R2 = 0.96), whereas the incidence of nonsurgical treatment increased from 63.9% to 68.7% (R2 = 0.89). Hospitals in the top treatment volume quartile (quartile 1 Q1; n = 29) had a lower rate of positive margins (16.3%) than bottom‐quartile centers (n = 741; rate of positive margins, 36.4%; P < .001); Q1 hospitals used surgical therapy significantly more. Independent predictors of nonsurgical therapy included older age, advanced disease, lower hospital volume, and living closer to the hospital or outside the Pacific United States. In surgically treated patients, younger age, lower hospital volume, nodal disease, positive surgical margins, and extranodal extension (ENE) also predicted more adjuvant CRT use. Conclusions The use of upfront surgical treatment decreased from 2010 to 2014. Hospital volume shows a strong, inverse correlation with the rate of positive surgical margins. The upfront treatment strategy is predicted not only by staging but also by patient‐, geographic‐, and hospital‐specific factors. Lower hospital volume remains independently associated with increased triple‐modality therapy after adjustments for positive margins, ENE, and pathologic staging. There is significant national treatment variability for human papillomavirus–mediated oropharyngeal cancer, and the utilization of both surgery with chemoradiation and upfront surgical approaches overall is decreasing. In addition to disease‐specific variables, numerous patient‐ and hospital‐specific variables play an important role in the upfront treatment strategy and the receipt of adjuvant chemoradiation.