The gas-phase thermal decomposition of a series of alkyl t-butyl ethers catalyzed by hydrogen chloride is theoretically studied at the ωB97XD/6-311++g(d)//CCSD(T)/6-311++g(d) level. The experimental activation free energy for three known systems namely: t-butyl methyl ether, t-butyl ethyl ether, and t-butyl isopropyl ether is used for validation of the proposed theoretical model as the transition state (TS). The chemical process was characterized using intrinsic reaction coordinate, reaction force, and reaction electronic flux profiles. The Cαδ+-Oδ− polarization was identified as the determining factor in the rate-limiting step. Upon functionalization on the Cα, 24 new compounds with different electron-withdrawing and donating groups were studied. A good multiple-linear correlation (R2 = 0.88) was found between the Ln(kX/kH) as the response variable and the Taft-Topsom substituent parameters as attributes. This result supports the reliability and predictability of the proposed transition state model at this level of theory.