Background: To define the chronological changes of long-term survival among patients with non-hepatitis-related hepatocellular carcinoma (Non-Hep-HCC) versus hepatitis C-related HCC (HCV-HCC) over the last two decades. Methods: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. Overall (OS) and recurrence-free survival (RFS) were analyzed and compared among Non-Hep-HCC versus HCV-HCC patients. Propensity score matching (PSM) was utilized to mitigate residual bias. Results: Among 617 patients, 196 (31.8%) patients had HCV-HCC, whereas 421 (68.2%) patients had Non-Hep-HCC. While patients with HCV-HCC had an improvement in OS over time (5-year OS, 2000–2009 55% vs. 2010–2017 67%, p = 0.034), OS among patients with Non-Hep-HCC remain unchanged (5-year OS, 2000–2009 53% vs. 2010–2017 52%, p = 0.905). In the matched cohort, patients with HCV-HCC had a worse OS versus patients with Non-Hep-HCC during 2000 and 2009 (5-year OS, 12% vs. 63%, p = 0.029), but significantly better OS from 2010 to 2017 than patients with Non-Hep-HCC (5-year OS, 86% vs. 73%, p = 0.035). The recurrence timing, patterns and re-treatments were comparable among Non-Hep-HCC and HCV-HCC patients. Conclusion: While OS of patients with HCV-HCC improved over time, the long-term survival of patients with Non-Hep-HCC patients remained unchanged and was more unfavorable.