Semiconducting conjugated polymers, such as P3HT, have applications for photovoltaic and flexible electronics. However, charge transport is sensitive to the mechanical behavior of the donor P3HT. A computational framework has, therefore, been used to identify the microstructural mechanisms, at different physical scales, that affect behavior. The approach accounts for the microstructure as an interrelated three-phase model that is physically representative of crystalline domains, an amorphous interphase, and tie-chain bridging regions. Based on our predictions, the face-on packing crystalline orientations had higher toughness in comparison with the edge-on packing orientations that had higher strengths due to local dislocation-density interaction mechanisms. The higher inelastic deformation, associated with face-on orientations, disrupted the conjugation structure in the crystalline phase, and this could affect charge. These predictions indicate that the behavior of P3HT polymers can be optimized by controlling the packing orientations, the crystallinity, the entangled chain density, and the tie chain interconnectivity. (C) 2014 Elsevier Ltd. All rights reserved.