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Background: Prostate cancer (PCa) is the leading malignancy among Ghanaian men, often diagnosed at an advanced stage due to limited screening, delayed presentation, and constrained diagnostic resources. Understanding the sociodemographic and clinicopathological determinants of disease severity is essential for improving early detection and outcomes. Objective: To examine the distribution and associations between sociodemographic, lifestyle, family history, and clinical factors with key clinicopathological features—PSA, DRE risk category, ISUP grade, D’Amico classification, and bone metastases—in Ghanaian prostate cancer patients. Methods: This cross-sectional analytical study retrospectively reviewed 258 histologically confirmed PCa cases. Data on sociodemographic, lifestyle, family history, and clinicopathological variables were extracted. Descriptive statistics summarised distributions; chi-square tests assessed bivariate associations; and multivariable logistic regression identified independent predictors of adverse disease. Statistical significance was set at p < 0.05. Results: Patients were predominantly aged 45–87 years (68.7%), with 71.7% having PSA ≥20 ng/mL, 45.3% high risk DRE findings, 32.6.% high risk ISUP grade (≥4), 80.6% in the high-risk D’Amico category, and 38% with bone metastases. Educational level, religion, bone pain, and pathological variables—including ISUP grade (χ² = 66.50, p < 0.001), DRE risk (χ² = 34.85, p < 0.001), ALP (χ² = 168.33, p < 0.001), percentage of cores involved (χ² = 40.12, p = 0.029), and perineural invasion (χ² = 7.505, p = 0.029)—showed significant associations with adverse features, while ethnicity, occupation, family history, smoking, and prostate volume were not significant. PSA was strongly associated with ISUP grade, DRE risk, and D’Amico classification. Multivariable analysis identified education, religion, bone pain, ISUP grade, DRE risk, ALP, and percentage of cores involved as independent predictors of severe disease. Conclusion: Prostate cancer in Ghana is characterised by late-stage presentation, high PSA, aggressive histology, and substantial metastatic burden. Targeted community education, earlier screening, and risk-based clinical assessment incorporating sociodemographic and pathological predictors are critical for improving detection and outcomes in resource-limited settings.