© 2020 Elsevier B.V.A crystal plasticity based finite element (CPFE) framework is developed for performing representative volume element (RVE) calculations on two-phase materials. The present paper investigates the mechanical response and the evolution of microstructure of dual-phase (DP) steels under uniaxial tensile loading, with a special focus on void nucleation. The spatial distribution and morphology of the ferrite and martensite grains in DP steels are explicitly accounted for by generating three-dimensional RVEs with Voronoi tessellations. The effects of microstructural parameters—the volume fraction, morphology and spatial distribution of the martensite phase, and the grain size and orientation distribution of the ferrite phase—on the initiation and spread of localized plastic deformation (leading to void nucleation) are investigated in detail. The soft ferrite phase is modelled by a local crystal plasticity theory with anisotropic elasticity, and the hard martensite phase by the J2 flow theory with isotropic elasticity. The developed CPFE framework successfully predicts both the overall and the local mechanical response, and is perfectly capable of distinguishing between different void nucleation mechanisms experimentally observed for DP steels.