Background: Medicaid expansion through the Affordable Care Act (ACA), implemented by 26 states in January 2014 and 13 more states in later years, has been shown to improve insurance coverage and early diagnosis of cancer in young adults (YAs). Little is known about whether these improvements translate to a survival benefit in this population. We evaluated the association between the ACA Medicaid expansion and 2-year overall survival among YAs newly diagnosed with cancer. Methods: Using the National Cancer Database, we identified 345,414 YAs aged 18-39 years diagnosed with cancer between 2010 and 2017. YAs diagnosed pre-expansion were followed through September 30, 2013 or three months before Medicaid expansion implementation for late-expansion states, and YAs diagnosed post-expansion were followed through December 31, 2019. We applied the difference-in-difference (DD) method to estimate changes in 2-year overall survival before and after Medicaid expansion, in expansion- versus non-expansion states, controlling for key sociodemographic factors. DD analyses were performed for YAs overall, and stratified by cancer type, stage at diagnosis, race/ethnicity, comorbidity, and facility type. Results: Among all YAs, 2-year overall survival increased more in expansion states (90.39% pre-expansion to 91.87% post-expansion) than in non-expansion states (88.98% pre-expansion to 90.05% post-expansion), resulting in a net increase of 0.53 percentage points (ppt; 95% confidence interval [CI] = 0.11 to 0.95 ppt). The increase in 2-year overall survival in expansion states versus non-expansion states was greatest among subgroups of patients with female breast cancer (DD = 1.20 ppt; 95% CI = 0.28 to 2.13 ppt) and patients with stage IV disease at diagnosis (DD = 2.51 ppt; 95% CI = 0.28 to 4.74 ppt). Additionally, greater improvement in 2-year overall survival associated with the expansion was seen among racial/ethnic minority YAs (including Hispanic, non-Hispanic Black, and non-Hispanic others; DD = 0.98 ppt; 95% CI = 0.10 to 1.86 ppt) than their non-Hispanic White peers (DD = 0.41 ppt; 95% CI = -0.06 to 0.89 ppt), among patients treated in community cancer programs (DD = 1.10 ppt; 95% CI = 0.32 to 1.88 ppt) than academic comprehensive cancer programs (DD = 0.12 ppt; 95% CI = -0.52 to 0.77 ppt), and among patients with two or more comorbidities (DD = 6.37 ppt; 95% CI = 0.68 to 12.06 ppt) than patients with no comorbidity (DD = 0.48 ppt; 95% CI = 0.04 to 0.91 ppt). Conclusions: We provide the first evidence on the association between ACA Medicaid expansion and improved overall survival among YAs newly diagnosed with cancer. Survival benefits are notable among racial/ethnic minority patients and patients with high healthcare needs, and by patients’ treatment facility type.