Nickel-based superalloys have become essential materials due to their excellent comprehensive properties as the miniaturization of products in the aerospace and energy fields develops. The complex microstructure and various strengthening mechanisms of nickel-based superalloys make the plastic deformation behavior extremely complicated at the mesoscopic scale. In this paper, compression experiments of nickel-based superalloy samples with different feature sizes (i.e. the sample diameter to grain size ratio, D/d) and different aging times at the mesoscopic scale were carried out. The coupling effect of feature size and δ phase on the compressive deformation behavior was studied. The results show that the δ phase plays a role in precipitation strengthening during compressive deformation at the mesoscopic scale. When D/d is in the range of 9.7–10.9, the flow stress decreases significantly with the increase of grain size, and a “smaller is weaker” size effect appears. When D/d is less than 9.7, the flow stress increases with the grain size, and a “smaller is stronger” size effect appears. Considering grain boundary strengthening, solid solution strengthening, and precipitation strengthening, a size effect model of flow stress was established. The calculated values were in good agreement with the experimental values. The inhomogeneity of the end surface and side surface increases with the decrease of feature size and the decrease of aging time. The presence of the δ phase reduces the inhomogeneous deformation of nickel-based superalloys during compressive deformation at the mesoscopic scale.