A test set 264 nucleophilic substitution reactions was studied via accurate quantum chemical reactions to establish the relative preferences for S(N)1 versus S(N)2 mechanisms. In low polar solvents, reactions involving anionic nucleophiles and leaving groups favored S(N)2 pathways. In contrast, S(N)1 is preferred for those reactions involving neutral nucleophiles and leaving groups except where the carbocation intermediates are exceptionally unstable. For neutral nucleophiles and anionic leaving groups, S(N)2 is generally preferred over S(N)1 except for exceptionally stable carbocation intermediates. On the basis of these studies, candidate reactions for which distinct S(N)1 or S(N)2 preferences could be reversed by electric fields were selected. As proof of concept, the S(N)1/S(N)2 preferences for the reaction of tBu-triflate with pyridine (S(N)2 to S(N)1) and with piperidine (S(N)1 to S(N)2) were switched by both charged functional groups and point charges (i.e., electric fields) along the reaction axis, with a positive charge on the nucleophile side favoring S(N)1 and a negative charge favoring S(N)2 for these reactions.