Women living with human immunodeficiency virus (HIV) have up to 6 times the risk of cervical cancer compared with HIV-negative women, with more than 60% of cervical cancer cases in Southern Africa occurring among HIV-positive women. Human papillomavirus (HPV) DNA self-sampling is a World Health Organization-recommended, cost-effective screening approach suitable for low-resource settings, particularly where healthcare worker availability and client mobility are constrained. With support from the Swedish Embassy, Population Services International Zimbabwe evaluated the feasibility and acceptability of HPV DNA self-sample collection among women of reproductive age, and assessed whether self-collected vaginal swabs yielded results comparable to provider-collected cervical samples. A quantitative cross-sectional crossover trial was conducted from May 2020 to December 2022 across three high-volume healthcare facilities. Women aged 30–65 were randomized into two arms: Arm 1 (self-collection followed by provider collection) and Arm 2 (provider collection followed by self-collection). Data were collected electronically using SurveyToGo and analyzed in STATA 13. Randomization checks assessed demographic comparability between arms. HPV positivity rates and 95% confidence intervals (CIs) were also computed. Among 609 self-collected samples, 26.9% were HPV-positive (95% CI: 23.5–30.6), compared with 29.3% positivity (95% CI: 25.8–33.0) among 611 provider-collected samples, showing statistically similar outcomes. Findings were consistent across study sites and participant age groups. Self-sample collection was widely acceptable among participants and deemed feasible by service providers. The results demonstrate that women can reliably self-collect samples for HPV DNA testing. This strategy offers a scalable, resource-efficient approach to expanding cervical cancer screening coverage in high-HIV–burden, low-resource settings, such as Zimbabwe, while reducing provider workload and facilitating earlier detection.