Background: High risk human papillomavirus (hr-HPV) infection and the dual burden of HIV remains a huge challenge in some low-income countries (LICs) such as Swaziland with limited or no data. We estimated the prevalence and investigated determinants of hr-HPV, including HIV infection among sexually active women in Swaziland. Methods: A total of 655 women aged between 15 and 49 years from five health facilities were randomly enrolled using a cross-sectional study design. Cervical cells were tested for hr-HPV types using GeneXpert HPV Assays. Results: The overall weighted hr-HPV prevalence was 46.2% (95%CI: 42.8-49.5). Of hr-HPV infected women, 12.4% (95%CI: 8.6-17.5) were HPV16-positive, 13.8% (95%CI:12.0-15.8) were positive for HPV18/45, 26.7% (95%CI: 24.2-29.3) for HPV31/33/35/52/58, 7.6% (95%CI: 7.6-11.9) for HPV51/59 and 11.0%, (95%CI: 7.9-15.3) for HPV39/56/66/68. Prevalence of hr-HPV decreased with increasing age. Overall HIV prevalence remained high (42.7%; 95%CI: 35.7-46.2). HIV infection was associated with hr-HPV infection (Adjusted OR = 4.9, 95%CI: 3.043-7.8, p<0.001). Overall hr-HPV/HIV co-infection was 24.4% (95% CI: 20.3-29.1) which was significantly higher among younger age groups (p<0.001). Prevalence of multiple group hr-HPV infection was significantly higher in HIV-positive versus-negative women (27.7% and 12.7% respectively, p<0.001). The presence, absence or unknown of history of STI with HIV did not appear to modify the relationship with hr-HPV (OR = 4.2, 95%CI: 2.6-7.1, OR = 4.6, 95%CI: 2.8-7.7, p<0.001, p<0.001 and OR = 4.1, 95%CI: 1.3-13.4, p<0.021 respectively). Conclusion: The prevalence of hr-HPV infection was high and significantly associated with HIV among sexually active women. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections which may explain the high prevalence among HIV infected women. This can contribute to policy development and planning of prevention strategies incorporating HPV infection prevention especially among youth and HIV infected people.