Cognitive dysfunction (CD) is recognized by the American Cancer Society as a treatment effect in head and neck cancer, but the extent of this problem at baseline in oropharyngeal cancer (OPC), the most common subsite in current practice, to our knowledge has never been studied. To assess the baseline cognition of patients with OPC using National Institutes of Health (NIH)-sponsored instruments of Patient-Reported Outcomes Measurement Information System (PROMIS) and NIH Toolbox Cognitive Battery (NIHTB-CB). This was a prospective cohort study conducted at a tertiary academic center. Of 83 consecutive patients, newly diagnosed as having OPC from September 2016 to May 2017, 16 were ineligible, 8 refused to participate, and 3 were lost to follow-up after screening, resulting in 56 study participants. Self-perceived and objective cognition with PROMIS and NIHTB-CB standardized T scores, respectively, were main outcomes. Impairment was defined as (1) T scores less than 0.5 SD for PROMIS; (2) T score less than 1.5 SD in at least 1 cognitive domain or less than 1 SD in 2 or more domains for NIHTB-CB total cognition; and (3) T score per previously published criteria for NIHTB-CB intelligence-stratified cognition. Of the 56 study participants (52 men, 4 women; median age, 59 years range, 42-77 years), 19 (34%) had a college degree, and 20 (36%) had a professional or technical occupation. Thirty (about 53%) were never-smokers, 26 (46%) were never-drinkers, 29 (52%) were obese, 13 (23%) had a moderate to severe comorbidity, 3 (5%) used antidepressants, and 25 (52%) had hearing loss. Impaired self-reported, NIHTB-CB total, and intelligence-stratified cognition scores were observed in 6 (11%), 18 (32%), and 12 (21%), respectively. Among all variables, objective impairment was more common in men (23% vs 0%) and those with p16-negative OPC (33% vs 20%), moderate to severe comorbidity (31% vs 18%), and hearing loss (31% vs 12%). Impaired objective cognition was more common at baseline than self-reported, and was more frequent in men, participants with p16-negative OPC, moderate to severe comorbidity, and hearing loss. NIHTB-CB allowed immediate scoring of demographically adjusted cognitive function. In clinical practice, these scores can be used to identify patients with impaired cognition at baseline who may be susceptible to developing further impairment after treatment. Identification of impairment at baseline will help to institute early cognitive interventions, which may lead to an improved posttreatment quality of life.