Background <p>Ghana has consistently reported a high perinatal mortality rate. This has raised concerns regarding the country’s ability to achieve the Sustainable Development Goals 3 target 2 by 2030. This comprehensive review presents the pooled prevalence and predictors of perinatal mortalities in Ghana guided by the Anderson’s framework of healthcare utilization.</p> Methods <p>A comprehensive literature search was conducted mainly from four electronic databases; PubMed, Web of Science, Scopus and CINAHL as they collectively index &gt; 90% of relevant maternal health journals in Africa and also eases the burden of screening. Eligible studies, published from 1st January 2010 to 30th June, 2024, were charted and synthesized, with focus on the three primary domains of Anderson’s framework: pre-disposing factors, enabling factors and need factors. Meta-analysis was conducted to estimate the pooled prevalence of perinatal mortality rate within each of the sub-regions. Significant heterogeneity was detected among the various surveys (I2 &gt; 50%), hence a random effect model was reported. Sub-group and meta-regression were performed to identify the sources of heterogeneity observed in the study.</p> Results <p>A total of 2,184 articles were initially identified for review, but after multiple rounds of screening and deduplication, only 30 full-text articles were finally included. The most frequent study design was cross-sectional, accounting for 23.3% of the studies. The Pooled estimate of perinatal mortality is 44.8 (95%CI: 15.4–74.2) per 1000 births in Ghana, with very high heterogeneity (I² &gt; 99.97, <i>p</i> &lt; 0.0001) among the studies. The predictors of perinatal mortality included advanced maternal age, pre-existing health conditions, poor quality ANC, access to healthcare facilities and environmental exposures.</p> Conclusion <p>This review presents the complex interplay of factors determining perinatal mortality in Ghana. In addition to the predictors identified, the review reveals gaps in literature particularly the lack of case-control studies in rural settings and inadequate focus on healthcare quality, socio-economic influences, and policy impacts. Future studies should address these gaps using a holistic approach that takes into account Ghana’s diverse social and geographical factors to better reduce perinatal mortality.</p> Systematic Review Registration. <p>The review protocol was registered in PROSPERO (CRD42024564968).</p>