ZSM-5, HY, and β zeolites were tested for cracking supercritical dodecane (SCD) in the presence and absence of supercritical water (SCW). A key experimental advantage of operating at supercritical conditions is that SCW and SCD are completely miscible, eliminating uncertainty introduced by liquid-liquid mass transport. As expected, all three zeolites were active in the absence of SCW, resulting in 70–80% dodecane conversion after 2 h at 400 °C. In the presence of SCW, only ZSM-5 retained activity, with a measured dodecane conversion of approximately 35%. Post-reaction characterization of the zeolites indicated that only ZSM-5 retained crystallinity, suggesting that access to acid sites decreases when the Y and β zeolites decrystallize. Although ZSM-5 retained crystallinity after exposure to the SCD/SCW reaction mixture, its BAS density decreased by >95% and its micropore area decreased by 80%. Interestingly, while the SCW environment decreases ZSM-5 activity, the reduction is not consistent with the magnitude of the reduction in BAS or micropore area. The apparent contradiction suggested that some material other than ZSM-5 may play the role of catalyst and extensive tests were performed to verify that acid sites on ZSM-5 remained catalytically active in the presence of SCW. Catalyst reuse experiments indicated that ZSM-5 can be reused in SCW. Additional tests with Na-ZSM-5, silicalite, alumina, coke, silicic acid, Al(NO3)3, HNO3, and the supernatant liquid recovered after reaction failed to identify any material other than ZSM-5 that could act as a catalyst. Therefore, ZSM-5 must act as an acid catalyst, even in the presence of SCW and despite loss of many of its acid sites. In contrast, HY and β do not. This work helps guide future work on the use of zeolites in the presence of liquid water and dense supercritical water phases.