Background: Cervical cancer is a major global health issue, with 89% of cases occurring in low- and middle-income countries (LMICs). Human papillomavirus (HPV) self-sampling tests have been suggested as an innovative way to improve cervical cancer screening uptake and reduce the burden of disease. The objective of this review was to examine the effect of HPV self-sampling on screening uptake compared to any healthcare provider sampling in LMICs. The secondary objective was to estimate the associated costs of the various screening methods. Method: Studies were retrieved from PubMed, Embase, CINAHL, CENTRAL (by Cochrane), Web of Science, and ClinicalTrials.gov up until April 14, 2022, and a total of six trials were included in the review. Meta-analyses were performed mainly using the inverse variance method, by pooling effect estimates of the proportion of women who accepted the screening method offered. Subgroup analyses were done comparing low- and middle-income countries, as well as low- and high-risk bias studies. Heterogeneity of the data was assessed using I 2. Cost data was collected for analysis from articles and correspondence with authors. Results: We found a small but significant difference in screening uptake in our primary analysis: RR 1.11 (95% CI: 1.10–1.11; I 2 = 97%; 6 trials; 29,018 participants). Our sensitivity analysis, which excluded one trial that measured screening uptake differently than the other trials, resulted in a clearer effect in screening uptake: RR: 1.82 (95% CI: 1.67–1.99; I 2 = 42%; 5 trials; 9590 participants). Two trials reported costs; thus, it was not possible to make a direct comparison of costs. One found self-sampling more cost-effective than the provider-required visual inspection with acetic acid method, despite the test and running costs being higher for HPV self-sampling. Conclusion: Our review indicates that self-sampling improves screening uptake, particularly in low-income countries; however, to this date, there remain few trials and associated cost data. We recommend further studies with proper cost data be conducted to guide the incorporation of HPV self-sampling into national cervical cancer screening guidelines in low- and middle-income countries. Systematic review registration: PROSPERO CRD42020218504. © 2023, The Author(s).