Background: Understanding factors that facilitate parents’ decisions to vaccinate their adolescents against human papillomavirus (HPV) is essential for improving vaccination coverage, particularly in low-resource settings where uptake remains low. Aims: This study aimed to determine facilitators of HPV vaccine uptake among parents of adolescents in Kaduna North Senatorial District, Nigeria, and evaluate the effect of a community-based nurse-led health education intervention. Methods: A quasi-experimental pretest–posttest study with intervention and control groups was conducted among 204 parents. The intervention group received structured community-based nursing health education, while the control group received routine information. Data were collected at baseline and 3 months (12 weeks) post-intervention using a structured questionnaire. Within-group changes were analyzed using McNemar tests and paired t-tests, while between-group comparisons used independent t-tests. Results: Significant improvements were observed in the intervention group in healthcare provider recommendation, perceived vaccine importance, access to reliable information, knowledge of HPV, perceived benefits, trust in the vaccine, and peer influence (p < .05). Mean facilitator scores increased significantly in the intervention group (7.41 ± 1.60 to 8.94 ± 2.20; p < .001), with no significant change in the control group. Conclusion: Community-based nurse-led health education strengthened key facilitators of HPV vaccine uptake among parents, and integrating structured HPV education into community nursing practice may enhance vaccination acceptance in underserved populations.