Exceptionally stable, mechanically robust, and highly methanol‐selective organosilica membranes, including Bis(triethoxysiyl)acetylene (BTESA), fluorine‐doped bis(triethoxysiyl) methane (F‐BTESM), and Cetyltrimethylammonium chloride‐etched bis(trimethoxysiyl)hexane (CTAC‐BTMSH), were prepared and utilized for organic solvent reverse osmosis (OSRO) separations. The BTESA membrane showed optimal separation performance regarding methanol/toluene and possessed the highest levels of both permeation flux and rejection. Continuous measurements were performed to highlight the molecule size/shape discrimination of BTESA membranes using compounds such as methanol/methyl acetate, methanol/dimethyl carbonate (DMC) and methanol/methyl tert‐butyl ether (MTBE). Also, a generalized solution‐diffusion model was successful in predicting the permeation behaviors through organosilica membranes when used in an OSRO modality, and proved to be capable of accurate predictions on pressure‐dependent permeation flux and rejection for a wide range of feed concentrations (0–55 wt%) and pressures (2–14 MPa). This study lends important insight for the development of organosilica membranes and process design for the energy‐efficient OSRO separation of organic liquids.