Background: This study aims to assess the sex disparities in clinical characteristics and synchronous distant metastasis occurrence at diagnosis, as well as the subsequent prognosis in non-sex-specific cancers. Methods: The study included details from patients diagnosed with non-sex-specific cancers, during the period from 2010 to 2016, in the Surveillance, Epidemiology, and End Results (SEER) program. The distant metastasis prevalence and subsequent survival time were summarized in the total population and the population with specific cancers of different systems. The multivariable logistic and the Cox proportional hazards regressions were applied to evaluate the sex effect on distant metastasis occurrence and prognosis. The results were combined using meta-analysis. Results: Across all non-sex-specific cancers, the pooled prevalence of distant metastasis was 15.2% (95% CI: 14.7-15.7%) and 7.1% (95% CI: 6.8-7.3%) for males and females, respectively. The pooled median survival time was 8.40 months (95% CI: 7.99-8.81) for male patients and 9.40 months (95% CI: 8.84-10.02) for female patients. After combining all non-sex-specific cancers, male patients displayed a higher distant metastasis occurrence than females (pooled OR=1.06, 95% CI: 1.04-1.08; P<0.01), as well as worse overall survival after distant metastasis (pooled HR=1.08, 95% CI: 1.05-1.10; P<0.01). The sex differences were more significant in patients younger than 65 years (P<0.01). Additionally, the sex influence on prognosis was most predominant amongst patients from Asian or Pacific Islander ethnic groups. Conclusion: Male gender appears to be an independent risk factor associated with the occurrence and prognosis of synchronous distant metastasis. Therefore, sex-specific preventions and treatments should become the focus of future research.