The authors report a significant dependence of the morphology and charge carrier mobility of poly(2,5-bis(3-dodecylthiophene-2-yl)thieno[3,2-b]thiophene) (pBTTT) films on the substrate surface chemistry upon heating into its liquid crystal phase. In contrast with films on bare silicon oxide surfaces, pBTTT films on oxide functionalized with octyltrichlorosilane exhibit substantial increases in the lateral dimensions of molecular terraces from nanometers to micrometers, increased orientational order, and higher charge carrier mobility. The large-scale crystallinity of this polymer plays an important role in the high carrier mobility observed in devices, but renders it more sensitive to substrate surface chemistry than other conjugated polymers.