The present work focuses on a comprehensive density functional theory (DFT) study of newly discovered base-catalyzed substrate-controlled dimerizations of aliphatic alkynones. In order to understand the origin of selectivity of the cascade assemblies of 6-methylene-5-oxaspiro[2.4]heptanones and 2-alkenylfurans, structural and electronic properties of neutral and deprotonated alkynone molecules, thermodynamic and kinetic characteristics of the deprotonation of alkynones having diverse C-H active substituents at the carbonyl function under the action of a base, and thermodynamic and kinetic characteristics of possible mechanisms of the discussed cascade reactions were theoretically assessed. The obtained computational results have confirmed and clarified an early qualitative assumption on the key role of the nature of the aliphatic substituent. Apart from fully rationalizing the experimental results, the theoretical DFT data give valuable details and data for predicting the outcome of related base-catalyzed reactions between various electrophilic substrates and nucleophilic species formed from C-H active aliphatic alkynones.