Tobacco use and oral sex (OS) are important risk factors for oral and oropharyngeal Human papillomavirus (HPV) infection. Little is known about the prevalence of OS practice in South Africa. This study aimed to determine the prevalence of OS practice and tobacco use in a South African patient population. This cross-sectional study used a structured questionnaire to collect socio-demographic characteristics, tobacco use, betel nut use and OS practice data from consenting adults (18 years; n = 850). Oral sex practices were recorded for patients 18–45 years-old (n = 514). Data analysis included chi-square and multiple logistic regression analyses. Of the study population, 55.2% (n = 468) were female, 88% (n = 748) self-identified as black Africans and 45.1% (n = 383) were unemployed. Furthermore, 19.7% (n = 167), 6.4% (n = 54) and 2.1% (n = 18) were current smokers, snuff users and betel nut users, respectively. Out of the 514 who answered the questionnaire in relation to OS, 22.8% (n = 115) reported to practice it. Oral sex practice in the age group 18–45 years was most common among the self-identified white participants (41.9% and among tobacco users than among non-tobacco users (30.9% vs. 20.5%; p = 0.022). A multivariable-adjusted regression model showed that white South Africans were more likely to use tobacco than black Africans (OR = 5.25; 95% CI = 2.21–12.47). The practice of OS was more likely among those 18–35 years-old (OR = 1.67; 95% CI = 1.01–2.74), but had no significant association with tobacco use (OR = 1.06; 95% CI = 0.62–1.83). The observed age and ethnic differences in both risk behaviours suggest a need for targeted population intervention in order to reduce the risk for oral HPV infection.