Hexafluorobenzene and many of its derivatives exhibit a chemoselective photochemical isomerization, resulting in highly strained, Dewar-type bicyclohexenes. While the changes in absorption and emission associated with benzene hexafluorination have been attributed to the so-called “perfluoro effect”, the resulting electronic structure and photochemical reactivity of hexafluorobenzene is still unclear. We now use a combination of ultrafast time-resolved spectroscopy, multiconfigurational computations, and non-adiabatic dynamics simulations to develop a holistic description of the absorption, emission, and photochemical dynamics of the 4π-electrocyclic ring-closing of hexafluorobenzene and the fluorination effect along the reaction coordinate. Our calculations suggest that the electron-withdrawing fluorine substituents induce a vibronic coupling between the lowest-energy 1B2u (ππ*) and 1E1g (πσ*) excited states by selectively stabilizing the σ-type states. The vibronic coupling occurs along vibrational modes of e2u symmetry which distorts the excited-state minimum geometry resulting in the experimentally broad, featureless absorption bands, and a ∼100 nm Stokes shift in fluorescencein stark contrast to benzene. Finally, the vibronic coupling is shown to simultaneously destabilize the reaction pathway toward hexafluoro-benzvalene and promote molecular vibrations along the 4π ring-closing pathway, resulting in the chemoselectivity for hexafluoro-Dewar-benzene.