Background Human papilloma virus (HPV) infection forms a major etiological factor for oropharyngeal cancer (OPC), which has exhibited increased global incidence. Aim To compare the knowledge regarding HPV, its association with OPC, and HPV vaccine among students from different countries, years of the undergraduate program, and gender. Methods The current multinational cross-sectional study was conducted in 886 undergraduate dental students from Egypt, India, Pakistan, Saudi Arabia, UAE, and Sudan through Google survey forms from July 2021 to September 2021. The survey form comprised 27 items divided into four sections. The answers to the questionnaire were compared among students from different countries, different years of the undergraduate program, and males and females. Chi-square test was used to evaluate the correlation between the demographic characteristics of students and their knowledge regarding HPV and OPC. Results Females exhibited a better knowledge regarding knowledge and perception on HPV vaccine, whereas males exhibited a better knowledge regarding HPV and its correlation with OPC, and these differences were statistically significant (P < 0.05). The third- and fourth-year undergraduate students displayed a higher awareness of OPC and its connection with HPV than other year students, and this variance was found to be statistically significant (P < 0.001). Third-year and internship students exhibited a more positive attitude and comfort regarding the vaccine and discussing the same with patients than the other educational-level students. Students from India exhibited better knowledge about HPV and its association with OPC than the students from other countries, and this difference was statistically significant (P < 0.001). Conclusion Disparities in knowledge regarding HPV-related oral cancer have been detected among the female and male participants among different nations. From the entire study population, Indian students exhibited better knowledge regarding HPV. Females from all the nations exhibited a more positive attitude and comfort regarding the vaccine and discussing the same with patients than males. The results of this necessitate intervention measures including training workshops and awareness campaigns. Improving their knowledge regarding the same may increase their awareness, resulting in better patient care.