High-risk human papillomavirus (hrHPV) genotype is needed for adequate cervical cancer screening and HPV vaccination program evaluation as recommended by different guidelines. We aimed to assess the rate of HPV infection and HPV genotype distribution using vaginal self-sampling in a cohort of unscreened reproductive-age women in Ethiopia. A community-based cohort study was conducted with women aged 23-46 living in Adama, Ethiopia. A total of 885 self-collected vaginal swabs were obtained and tested for hrHPV genotypes with the real-time polymerase chain reaction technique. The overall hrHPV prevalence was 21.1% (187/885, 95% confidence interval [CI]: 18.5-24.0). Among women living with human immunodeficiency virus, 46% (30/56) (95% CI: 33.7-59) were hrHPV positive compared with 19% (157/820) (95% CI: 16.2-22) of human immunodeficiency virus-negative women. The most frequent genotypes were HPV16 (3.1%), HPV51 (3.1%), HPV35 (2.6%), HPV56 (2.6%), HPV52 (2.4%), HPV31 (2.5%), and HPV39 (2.5%). Among the 187 HPV-positive women in self-samples, HPV 16/18 was found in 21% (39), HPV 16/18/45 was found in 24% (44), and HPV 16/18/31/33/45/52/58 was prevalent in 56% (104). Out of 116 biopsies, 7% (8) had cervical intraepithelial lesions and worse identified. Of these eight cervical intraepithelial lesions and worse patients, only 25% tested positive for HPV-16; none tested positive for HPV-18 or 45. One out of five women tested positive for hrHPV genotypes. Other HPV genotypes not covered by the quadrivalent HPV vaccine but associated with clinically significant cervical high-grade lesions or cancer were detected in 75%. It is more effective to prevent cervical cancer by switching to the nine-valent HPV vaccine.