This study assessed university students' awareness and knowledge of human papillomavirus (HPV) and its vaccine and willingness to accept vaccination in Jeddah, Saudi Arabia, and identified factors associated with these outcomes. This cross-sectional study was conducted in Jeddah, Saudi Arabia. The study population included university-level male and female students. During the first term of the 2023-2024 academic year, eligible participants were sent an online questionnaire. The study variables included measures of sociodemographic factors, awareness and knowledge of HPV and its vaccine, and vaccine acceptance. We conducted descriptive analysis of awareness, good knowledge, and willingness to accept vaccination, and multivariable logistic regression analyses to determine predictors of these outcomes. The study included 400 participants with a mean age of 21.4years, predominantly female and of Saudi nationality (93%). Awareness of HPV infection was reported by 49.3% of participants, while 44% were aware of the HPV vaccine. Among those aware of HPV, 82.2% recognized its link to cervical cancer, but misconceptions about HPV exist. Only 3.8% of participants had been vaccinated for HPV, and 33.5% expressed willingness to accept the vaccine. Age (per 1year increment; OR: 1.42, 95% CI: 1.25 to 1.62,