Cyclic deformation of polycrystalline Ni-based superalloys leads to cyclic hardening followed by softening, in terms of the mechanical response. A micromechanical constitutive model is proposed and implemented in a dislocation density-based, crystal plasticity framework to simulate the shearing of γ′ precipitates, which leads to the observed cyclic softening. The framework accounts for physically based deformation mechanisms. A slip-system level backstress model has been implemented to account for the kinematic hardening. Further, a micromechanical model for microstructure evolution due to precipitate shearing is developed that accounts for the dislocation-precipitate interactions and the resultant change in precipitate strengthening. The model is used to simulate cyclic deformation in two polycrystalline Ni-based superalloys, with different microstructures (in terms of the shape, size and volume fraction of precipitates), referred as Alloy 1 and Alloy 2. Room temperature cyclic deformation tests, followed by microstructure characterization were performed at different strain amplitudes for Alloy 1 to validate our predictions. For Alloy 2, the experimental stress–strain response was used from the literature to fit and validate our predictions. It is shown that the model can predict cyclic softening due to precipitate shearing for different initial microstructures and a range of loading conditions in polycrystalline Ni-based superalloys.