The major objective of this investigation is to fundamentally understand and predict how intergranular (IG) and transgranular (TG) fracture modes nucleate and propagate in f.c.c. polycrystalline systems due to defects, such as total and partial dislocation densities and grain boundary (GB) structures and misorientations. A dislocation density crystalline plasticity (DCP) formulation based on the evolution and interaction of total and partial dislocation densities was integrated with a recently developed fracture approach to investigate the fracture nucleation and propagation of simultaneous multiple fracture events, including both IG and TG fracture events. The aggregate grains and GB orientations and morphologies are based on EBSD measurements that are representative of polycrystalline copper aggregates with a broad range of random high angle and low angle GBs. The predictions indicate that dislocation density pileups induce IG fracture due to interrelated stress, slip, and total and partial dislocation density accumulations and interactions for both high angle GBs (HAGBs) and low angle GBs (LAGBs). TG fracture nucleation and propagation occurred due to normal stress accumulations, which exceeds the fracture stress, along cleavage planes. Furthermore, it is shown how IG cracks transition from the GB plane to the cleavage planes as cracks nucleate and propagate. Accumulated plastic zones due to different slip system activities can impede and blunt crack propagation and fronts. These plastic zones form due to high Lomer and Shockley partial dislocation densities. These predictions, which are consistent with experimental observations, provide a fundamental understanding of how simultaneous failure modes initiate and propagate for physically representative microstructures.