In this study, the effects of varying crystal orientation and composition on active deformation modes are explored for two different Ni-base disk alloys. Understanding these effects will allow for improved predictive modeling and consequently faster advancements in Ni-base alloy development. In order to investigate these effects, compression creep tests were conducted on  and  oriented single crystal specimens of the disk alloys ME3 and ME501, at different stress/temperature regimes. At 760 °C and below, a prominent creep anisotropy exists between the two orientations, with the  oriented samples exhibiting superior creep strength. At 815 °C, the creep anisotropy disappeared between the two orientations. Through bright field scanning transmission electron microscopy, it was determined that the existence of creep anisotropy is a result of differences in deformation modes between the different orientations and alloy compositions. Results of phase field modeling in which the interaction of dislocations with realistic precipitate structures is also conducted to further advance predictive creep deformation models.