A novel approach was developed to select the optimal duration for solid solution heat treatment of Ni-based single-crystal (SX) superalloys based on the statistical analysis of γ′ phase size in the second-generation SX superalloys. The microstructure uniformity ω was introduced through the statistical analysis. The ω curves can be divided into three stages according to the statistical analysis: the significant change area, transition area, and steady state area. The transition area shows the optimal duration range for solution heat treatment of Ni-based SX superalloys. This approach was verified by measuring the γ′ rafting rate and testing the creep properties of alloys. Meanwhile, the accuracy of this approach was also validated through the fourth-generation Ni-based SX superalloys. This approach can effectively optimize the heat treatment and provide guidance for the design and engineering applications of SX superalloys.