Although diketopyrrolopyrrole (DPP) conjugated polymers have been successfully explored in fullerene organic photovoltaics (OPVs) with high power conversion efficiency (PCE), their nonfullerene acceptor organic photovoltaics (NFOPVs) remain less investigated. Herein, we developed DPPbased polymers containing monochlorinated bithiophene (DPP2ThCl and DPP2PyCl), where the DPP unit was flanked by either thiophene or pyridine, respectively. DPP2ThCl showed a more extended photoabsorption and lower exciton binding energy in comparison to DPP2PyCl. The OPVs of these polymers blended with ITIC, IT-4F, Y6, and PC 71 BM revealed a PCE of 5.15% for DPP2ThCl:Y6, whereas the other blend gave lower values (0.07−4.07%). The superiority of DPP2ThCl:Y6 was rationalized by its enhanced planarity and crystallinity, smooth layer morphology, a low Flory−Huggins interaction parameter, and improved charge transport characteristics. We further analyzed the PCEs of all the blends by using machine learning, which identified the offset of highest occupied molecular orbital energies of donors and acceptors as the most important property. These findings highlight the importance of the structural manipulation of DPP-based polymers to improve the PCE of NFOPVs.