The positional selectivity of ring opening of small, strained organic rings is often considered to be governed by the maximal release of ring strain. However, reactions under cationic conditions can lead to multiple products due to the intermediacy of non-classical carbocations (carbonium ions cations featuring a formally pentavalent carbon atom). A famous example is the solvolysis of cyclobutyl or cyclopropylmethyl derivatives, which proceed via two equilibrating non-classical carbocations the cyclopropylcarbinyl ion (CC), and the bicyclobutonium ion (BB) generating up to three products on nucleophilic capture. The utility of such reactions is therefore often limited, despite the value of the small ring products. Using bicyclo[1.1.0]butanes (BCBs) as a template, we show that the regiochemical outcome of small ring opening can be controlled by subtle changes to the structure of non-classical carbocation intermediates, in turn enabling the rational prediction of regioselectivity. We find that the regio- and stereochemistry of ring opening depends not only on the degree of substitution, but also the nature of the substituents, of the BCB ring system and its resulting cationic intermediate. We show that these outcomes can be rationalised by computational models, where bond lengths in the non-classical carbocation inform on the site of reaction. As BCBs are finding increasing use as tools in chemical synthesis and bioconjugation, understanding the factors that control their ring opening offers new opportunities for applications of these molecules. These findings also have consequences for the design of other chemical transformations that proceed through such non-classical intermediates.