Background <p>Sexually transmitted infections (STIs) remain a significant public health challenge in Ghana, with varying prevalence across regions and populations. A nationwide synthesis of STI burden and risk factors is lacking, hindering targeted interventions. This systematic review and meta-analysis examined STI prevalence, risk factors, and distribution patterns across the country, providing data to support SDG 3 and inform effective public health interventions.</p> Methods <p>We conducted literature searches using the PubMed repository and three databases: Scopus, Web of Science, and ScienceDirect. Eligible studies were observational studies that reported STI prevalence based on clinical diagnosis across Ghana. The quality of the included studies was assessed using standardized JBI checklists for prevalence studies. Random-effects meta-analysis with a 95% confidence interval was performed to estimate pooled prevalence and conduct subgroup analyses.</p> Results <p>The pooled STI prevalence was 7.5%. Urban areas exhibited the highest prevalence (9.06%) compared to rural areas (6.67%), likely reflecting differences in healthcare access, awareness, and risk behavior. Risk factors included multiple sexual partners, homosexuality, and needle sharing. Pathogen-specific analysis revealed higher prevalence rates for viral infections (8.03%) than bacterial infections (6.01%). Co-infections of both bacterial and viral infections had a prevalence of 10.88%. </p> Conclusions <p>STIs pose a substantial burden in Ghana, particularly among urban populations and high-risk groups. Key public health strategies – including outreach to high-risk groups, free preventive commodities, health systems strengthening, risk behavior education, and improved diagnostic approaches – are critical to addressing Ghana’s diverse STI burden and reducing prevalence.</p>