• Alkyl chains are used to control the molecular orientation and charge transport. • The size of alkyl chains on the nitrogen atoms directs the backbone orientation. • A record PCE of 15.63% among A-D-A-type acceptors with chlorinated end groups. • Edge-on orientation leads to a high transistor mobility of 3.95 × 10 −2 cm 2 V −1 s −1 . Control over the molecular orientation of organic semiconductors with respect to the substrate plays a critical role in determining the performance of organic electronic devices. In this work, three ladder-type heteroheptacene-based small molecules with branched or unbranched side chains flanked in different positions of their conjugated backbone (M11, M12, and M13), were designed and synthesized to investigate the effect of side-chains on the crystallinity, molecular orientation, and optoelectronic properties of the organic semiconductors. When linear n-dodecyl side-chains are attached to the nitrogen atoms of the heteroheptacene core, the resulting molecule (M11) exhibits high crystallinity and edge-on molecular orientation, thus leading to excellent horizontal charge transport with a field-effect transistor (FET) mobility of 3.95 × 10 −2 cm 2 V −1 s −1 . Replacing the linear n-dodecyl chains on the nitrogen atoms with the branched 2-butyloctyl chains leads to the organic semiconductors (M12 and M13) with the face-on dominated molecular orientation thereby leading to two orders of magnitude enhancement in the vertical charge transport in comparison with M11. Consequently, M12 and M13 show much higher power conversion efficiencies (PCEs) of 11.55% and 13.14%, respectively, compared to M11 which exhibits a PCE of 2.26% under the same device fabrication conditions. Optimization on the M13-based solar cells yields a further improved PCE of 15.63% which is among the highest values for the A-D-A type nonfullerene acceptors. The results reported in this work highlight that modulating the molecular orientation of organic semiconductors is a highly effective molecular design strategy to boost the performance of optoelectronic devices, thus also providing new insights into the molecular design guidelines for the next generation of high-performance semiconductors for the FET and photovoltaic applications.