CASPT2//CASSCF and B3LYP methodologies have been used to study the excited-state properties and photochemical isomerizations of p-, m-, and o-methylbenzonitriles and methylanisoles. Calculations show that the biradical mechanism is the most favored channel for the photoinduced interconversion of p-, m- and o-methylbenzonitriles, both dynamically and thermodynamically. The formation of biradical as a key intermediate is highly selective, and only the biradicals with a turned-up cyano-substituted carbon are involved in photoisomerization. Methylanisole isomers are inactive relative to methylbenzonitriles at 254 nm. Such remarkable activity difference between methylbenzonitrile and methylanisole in photochemistry arises from the accessibility of the S-1/S-0 conical intersection as well as the stability of prefulvene biradicals. For methylanisoles, the S-1/S-0 precursor and the reactive biradicals are inaccessible at 254 nm, which should be the origin of inactivity. The results suggest that the conical intersection accessibility plays a crucial role in the photochemistry of substituted benzenes at 254 nm.