The impact of acute liver dysfunction and chronic liver disease on adult patients receiving extracorporeal membrane oxygenation (ECMO) support remains unclear. To investigate this, we performed a retrospective analysis of the Extracorporeal Life Support Organization (ELSO) Registry using data from 2012 to 2023. We used generalized linear regression models (GLMs) to examine the associations between acute liver dysfunction, chronic liver disease, and survival to hospital discharge. A total of 4,915 ECMO runs were included in the analysis. Survival to hospital discharge was 34% for patients with acute liver dysfunction compared to 42% for those with chronic liver disease. Compared to patients with acute liver dysfunction, those with chronic liver disease were more likely to survive (~29% more likely). Increased age (odds ratio [OR] per year: 0.97, 95% confidence interval [CI] = 0.97–0.98, p < 0.001) and low bicarbonate levels (OR per unit: 0.79, 95% CI = 0.67–0.93, p = 0.005) were associated with lower odds of survival. There was no difference in ECMO-related complications based on liver dysfunction acuity. Patients with acute liver dysfunction and chronic liver disease both have unique challenges during ECMO; however, acute liver dysfunction appears to be disproportionately associated with poor outcomes. Further studies are needed to fully understand the impact of liver dysfunction on ECMO survival.