The morphology of the active layer in organic photovoltaics is critical in the optimization of device efficiencies. Most strategies aimed at improving morphology are focused mainly on annealing methods or the use of solvent additives. By using diketopyrrolopyrrole derivatives as donors and [6,6]-phenyl-C71-butyric acid methyl ester as electron acceptors, we report here on the effect of hydrogen bonding on active layer morphology and solar cell efficiency. We specifically compared two asymmetric derivatives, one containing an amide bond capable of forming hydrogen bonds with one containing an ester bond in the same position. Although both molecules have very similar optoelectronic properties, films of the ester revealed greater crystallinity and π-π stacking as characterized by grazing incidence X-ray diffraction. In great contrast, active layers formed with the amide derivative formed short fiber-like supramolecular aggregates with much smaller domain sizes and less order as characterized by atomic force microscopy and X-ray diffraction. Interestingly, devices fabricated with the amide-fullerene combination have a greater short circuit current (JSC) leading to a 50% increase in power conversion efficiency compared to devices formed with the ester derivative. We conclude that the effective competition of hydrogen bonding over extensive π-π stacking results in morphologies that lead to higher photovoltaic efficiencies.