Nickel-based single crystal superalloys CMSX-4 have been widely used to manufacture aeroengine turbine blades because of their excellent high-temperature comprehensive properties. The microstructure evolution behavior, mechanism, and influence on micromechanical behavior of the second-generation nickel-based single crystal superalloy during long-term aging at 950°C and 1050°C for 10–2000 h were investigated. The results show that, with the extension of aging time, the average size of γ' phase increased, whose morphology changed from square block to strip and L shape and rafting phenomenon was observed. The coarsening of γ' conforms to Lifshitz–Slyozov–Wagner (LSW) theory and the coarsening rates are 4.241×10−5 and 9.954×10−5μm3/h at 950°C and 1050°C, respectively. After aging at 950°C and 1050°C for 1000 h, segregation of refractory elements was formed in the samples. There are hard topological close-packed (TCP) phases surrounded by γ' envelope precipitates, which destroyed the continuous structure of γ'. The precipitation of TCP caused the depletion of refractory element Re in the γ' envelope phases, resulting in softening effect. It was also found that high temperature can not only accelerate the coarsening of γ' phase but also promote the precipitation and growth of TCP phases.