We report a three-dimensional (3D) molecular orientation control of a liquid crystal organic semiconductor (LC-OSC) based on the long-range ordering characteristic of an LC material. To this end, a synthetic LC-OSC molecule, MeOPh-BTBT-C8, with a fluidic nematic (N) phase that is essential for alignment control over a large area and a smectic E (SmE) phase showing high ordering, was prepared. A simple flipping of a sandwich cell made of the LC-OSC material between the top and bottom substrates that have uniaxial-planar degenerated alignment as well as crossed rubbing directions responds to the given surface anchoring condition and temperature gradient. Optical observation of the alignment-controlled LC-OSC was carried out by polarized optical microscopy (POM), and the corresponding charge carrier mobility was also measured by fabricating organic field-effect transistors (OFETs). Our platform offers a facile approach for multidirectional and multifunctional organic electronic devices using the stimulus-response characteristics of LC materials.