We present an unusual observation of facile single-crystal-to-single-crystal phase transition induced in hydrophobic silicone oil at ambient conditions which is fast in ortho-fluoro substituted ethynyl phenyl benzamide and relatively slow for the meta-isomer. These phase transitions are also observed in crystals, on heating, at high temperature, and in the absence of silicone oil. The extensive thermal and structural analyses reveal that the phase transition between the two polymorphs of the ortho-isomer is monotropic in nature and involves large supramolecular rearrangements, wherein for the meta-isomer the same is enantiotropic and is driven by altered molecular conformations. The structural features demonstrate the absence of prevalent and strong N—H···O═C hydrogen bonds in the crystal structures of both polymorphs of the ortho-fluoro substituted benzamide. A plausible molecular mechanism based on energetically favored “structural motifs” has been proposed which depicts that rotational and translationa...