Here, an effective design strategy of polymer thermoelectric materials based on structural control in doped polymer semiconductors is presented. The strategy is illustrated for two archetypical polythiophenes, e.g., poly(2,5-bis(3-dodecyl-2-thienyl)thieno[3,2-b]thiophene) (C12-PBTTT) and regioregular poly(3-hexylthiophene) (P3HT). FeCl3 doping of aligned films results in charge conductivities up to 2 × 105 S cm−1 and metallic-like thermopowers similar to iodine-doped polyacetylene. The films are almost optically transparent and show strongly polarized near-infrared polaronic bands (dichroic ratio >10). The comparative study of structure–property correlations in P3HT and C12-PBTTT identifies three conditions to obtain conductivities beyond 105 S cm−1: i) achieve high in-plane orientation of conjugated polymers with high persistence length; ii) ensure uniform chain oxidation of the polymer backbones by regular intercalation of dopant molecules in the polymer structure without disrupting alignment of π-stacked layers; and iii) maintain a percolating nanomorphology along the chain direction. The highly anisotropic conducting polymer films are ideal model systems to investigate the correlations between thermopower S and charge conductivity σ. A scaling law S ∝ σ−1/4 prevails along the chain direction, but a different S ∝ −ln(σ) relation is observed perpendicular to the chains, suggesting different charge transport mechanisms. The simultaneous increase of charge conductivity and thermopower along the chain direction results in a substantial improvement of thermoelectric power factors up to 2 mW m−1 K−2 in C12-PBTTT.