A new building block, 1,4-di(3-alkoxy-2-thienyl)-2,5-difluorophenylene (DOTFP) with several desirable features such as high backbone planarity, suitably lying highest occupied molecular orbital (HOMO), and good solubility, was developed by inserting an electron-deficient difluorophenylene into the 3,3'-dialkoxy-2,2'-bithiophene (BTOR) unit. Three regioregular D-A(1)-D-A2 type polymers based on DOTFP and benzothiadiazole (BT) derivatives were synthesized and characterized by comparing with a D-A type BTOR-based polymer. The content of highly electron-rich alkoxythiophene is reduced by half in the DOTFP-based polymers versus that of the BTOR-based polymer analogue, which results in a deeper HOMO level and benefits high open-circuit voltage (V-oc) in polymer solar cells (PSCs). Consequently, the DOTFP-ffBT-based solar cells exhibited a significantly improved power conversion efficiency (PCE) of 8.7% and an increased V-oc of 0.84 V compared to the BTOR-ffBT-based solar cells with a PCE of 2.6% and a V-oc of 0.49 V. Additionally, the DOTFP-based polymers showed improved charge transport properties and film morphology than the BTOR-based polymer BTOR-ffBT, resulting in simultaneous enhancement of the short-circuit current (J(sc)) and fill factor (FF) in PSCs. These results demonstrate the great promise of the DOTFP building block for the construction of high-performance photovoltaic polymer semiconductors with increased V(oc)s.