This paper presents results from a research initiative aimed at investigating high temperature creep deformation mechanisms in Ni-base superalloys through a combination of creep experiments, TEM deformation mechanism characterization, and state of the art modeling techniques. The effect of microstructure on dictating creep rate controlling deformation mechanisms was revealed for specimens with a bimodal γ' size distribution that possessed different secondary γ' size, tertiary γ' volume fraction, and γ channel width spacing. It was found that the less creep resistant microstructure was the one with a greater secondary γ' size, wider γ channel width, and higher volume fraction of tertiary γ'. Deformation in this microstructure commences by way of a/2 dislocations concentrated in the γ matrix at lower strains, which then transition to a SISF precipitate shearing mode at larger strains. The more creep resistant microstructure possessed a finer γ channel width spacing, which promoted a/2 dislocation dissociation into a/6 Shockley partials at lower strains and microtwinning at higher strains. Dislocation precipitate interaction was further explored using microscopic phase field modeling, which was able to capture key microstructural aspects that can favor dislocation dissociation and decorrelation since this appears to be a precursor to the microtwinning deformation mode. New viable diffusion pathways associated with the reordering processes in microtwinning have been explored at the atomistic level. All of the above activities have shed light onto the complex nature of creep deformation mechanisms at higher temperatures.