Background and Objectives: Persistent high-risk Human Papillomavirus (HPV) can cause cancers in the cervix, vulva, vagina, anus, penis, and oropharynx. A lack of knowledge about HPV can lead to vaccine hesitancy, which is detrimental to combating HPV-related diseases. This study aimed to assess the effectiveness of an HPV educational intervention to enhance university students' awareness of HPV. Materials and Methods: We conducted a quasi-experimental one-group pre-test and post-test study on male and female college students from the College of Applied Medical Science and the College of Nursing in Riyadh, Saudi Arabia, at King Saud University. Data were collected from May 2023 to March 2024. The first section of the survey assessed sociodemographic factors, and the second section measured knowledge regarding HPV. Results: A total of 271 students completed the surveys, with 71 males (26.2%) and 200 females (73.8%) participating. Students aged 22 years or older had better HPV awareness. Gender significantly predicts HPV awareness, with female students being four times more likely to be aware of HPV compared to male students. After the educational intervention, significant improvements in HPV knowledge were observed in all items (p-values < 0.0001) and across all demographic groups. Misconceptions about HPV were corrected, and the overall knowledge score increased from 29.3% to 82.0%. Conclusions: Our results suggest that similar interventions could benefit other populations in the kingdom, potentially increasing vaccination rates.