Background: Despite the human papillomavirus (HPV) vaccine being safe and effective at preventing HPV-associated cancers, vaccine update is low. Several factors have been identified as barriers to getting the HPV vaccine. However, it is unclear if these factors have changed since vaccine licensure. Thus, we assessed trends in the top five reasons for vaccine hesitancy in the last decade in the US. Methods: We analyzed the 2010–2019 National Immunization Survey–Teen data, a national survey representative of the US adolescent population. We identified adolescents (n = 16,383) who had received zero dose of the HPV vaccine (unvaccinated adolescents). Parents of unvaccinated adolescents were asked how likely they will vaccinate their child in the next 12 months. Parents who responded with “not too likely”, “not likely at all” or “not sure/don’t know” (vaccine hesitant) were asked what the reasons are for their hesitancy. The top five most cited reasons for vaccine hesitancy: “not necessary”, “safety concerns”, “lack of recommendation”, “lack of knowledge”, and “not sexually active” were included in the study. Joinpoint regression estimated yearly increases/decreases in these reasons using annual percent changes. Results: The proportion of unvaccinated adolescents whose parents cited “safety concerns”’ as a reason for HPV vaccine hesitancy decreased from 2010 to 2012 but increased significantly from 2012 to 2019 at an average of 8.6% annually. The proportion of unvaccinated adolescents whose parents cited “not sexually active” as a reason for HPV vaccine hesitancy decreased on average by 33.1% from 2010-2012 and then at an average of 11.5% in the remaining years. The proportion of unvaccinated adolescents whose parents cited “not necessary” as a reason for HPV vaccine hesitancy decreased from 2010-2012 but significantly decreased by an average of 11.0% yearly from 2012-2019. The proportion of unvaccinated adolescents whose parents cited “lack of recommendation” and “lack of knowledge” as reasons for HPV vaccine hesitancy decreased over the 10-year period though not statistically significant. Conclusions: There was a decrease in most of the reasons cited by parents for vaccine hesitancy except vaccine safety which has been increasing from 2012 to 2019. These findings suggest an urgent need to combat the rising sentiment of safety concerns among parents of unvaccinated children to increase HPV vaccine confidence.