Effect of duplex grain size distributions on long-term stress-rupture life of Nimonic 80A had been investigated. Non-homogeneous duplex grain size distributions greatly reduce stress-rupture life. Regional distribution of coarse grains is not good for acquiring high stress-rupture life, the formation of micro-void and propagation of cracking can easily occur at coarse grain boundary especially when plate-like Cr23C6 precipitates at grain boundary. But relatively homogeneous duplex grain size distributions are of great significance in improving stress-rupture life, the samples even possess the life value up to more than 13000 h especially when hardly any plate-like Cr23C6 precipitates at grain boundaries. Slightly increased Ti/Al ratio from 1.65 to 1.80 is also beneficial to obtain a significantly longer stress-rupture life value. The γ′ phase is very stable and always exhibits a coherent orientation relationship with γ on {100} and {111} atomic planes. The grain boundary cracking will not easily appear at the early stage of stress-rupture test in the samples with relatively homogeneous grain size distribution, the coarse and adjacent fine grains possess better deformation adjustability, and the grain boundary cracking is apparently wider and the number of cracking is also getting more after fracture for the sample with longer stress-rupture life.