The microstructure and high-temperature creep mechanisms of Ni-based Hastelloy C276 superalloy fabricated using wire and arc-based directed energy deposition were investigated systematically and innovatively. The microstructural investigation revealed that the as-fabricated samples comprise γ-Ni matrix and topologically close-packed (TCP) P phase precipitates. The γ matrix subgrains and grains are spread over multiple highly textured columnar dendrites, with a majority of γ <001> crystallographic orientations closely aligned along the deposition direction. Moreover, the interdendritic regions exhibit severe Mo segregation, P phase particles, and dislocation bands. Creep tests were conducted on miniature samples under various temperature and stress conditions, loaded either in the deposition direction (DD) or travel direction (TD). DD samples exhibit lower minimum strain rates, greater strains-to-failure, and longer creep rupture lifetimes than TD samples, indicating significant creep anisotropy. Dislocation creep was identified as the primary creep mechanism for both DD and TD conditions. During creep, dynamic precipitation of TCP phases occurred in the interdendritic regions, resulting in varying creep resistance between interdendritic and dendritic core regions. Isostress and isostrain models, considering both crystallographic texture and precipitation strengthening, reasonably predicted the observed creep anisotropy during the secondary creep stage. Additionally, variations in the Schmid factor led to significant deformation incompatibility among dendrites in TD samples. Dislocation accumulation in TD sample interdendritic regions promoted new grain nucleation, triggering dynamic recrystallisation, facilitating grain boundary sliding, and accelerating tertiary creep. Furthermore, TCP phase particles in the interdendritic regions contributed to microcrack development, further accelerating creep fracture, especially in the TD condition.