The thermally induced cyclodehydrofluorization of irontetrakis(pentafluorophenyl)porphyrin proceeds highly stereo‐selectively into a prochiral product on a gold surface in ultrahigh vacuum, whereas dehydrocyclization of the respective irontetrakisphenylporphyrin does not show such selectivity. Stereoselectivity is predominantly observed for closely packed layers, which is an indication of intermolecular cooperativity and steric constrain induced by adjacent species. Density functional theory identifies intermolecular packing constrain as origin of such selectivity during reaction. Scanning tunneling microscopy reveals enantiopure two‐dimensional self‐assembly of the reaction product into a conglomerate of mirror domains. On‐surface two‐dimensional topochemistry, as reported here, may open new routes to stereoselective syntheses.