Human papillomavirus (HPV) infects nearly 85% of sexually active Americans during their lifetime, causing most cervical and five other cancers. Routine HPV vaccination is recommended for adolescents to prevent HPV-attributable cancers, but HPV vaccination coverage remains low, especially in Tennessee. In 2021, 54.6% of the population in Shelby County, Tennessee was Black or African American, reporting higher rates of new cervical cancer cases than other counties in Tennessee. While medical and public health professionals (HPs) play a critical role in promoting vaccination coverage, little is known about the factors HPs perceive to influence HPV vaccination for this population. This study sought to explore HPs’ perceived facilitators and barriers of HPV vaccination among African American adolescents. Qualitative individual interviews with 26 HPs in Shelby County were conducted between October 2019 and February 2020. Interpretive content analysis of the interview data guided by the socio-ecological model revealed several important themes regarding the facilitators and barriers across the individual, interpersonal, and community levels. At the individual level, parental vaccine hesitancy emerged as a leading barrier to HPV vaccination, while appropriate education facilitated the vaccination. At the interpersonal level, a lack of strong provider recommendations impeded HPV vaccination, whereas improved communication skills with patients facilitated the vaccination. Finally, the community-level barriers included a lack of education and social/religious norms; the community-level facilitators included community outreach efforts. HPs should consider development of comprehensive community-based approaches that leverage the facilitators and barriers at multiple levels to increase HPV vaccination among African American adolescents in this region.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12913-023-09415-6.