Ethylene glycol (EG) produced from biomass is a promising candidate for several new applications. In this paper, EG derivatives such as mono- and di-tert-butyl ethers are considered. However, accurate thermodynamic data are essential to optimise the technology of the direct tert-butyl ether EG synthesis reaction or reverse process isobutene release. The aim of this work is to measure the vapour pressures and combustion energies for these ethers and determine the vaporisation enthalpies and enthalpies of formation from these measurements. Methods based on the First and Second Law of Thermodynamics were combined to discover the reliable thermodynamics of ether synthesis reactions. The thermochemical data for ethylene glycol tert-butyl ethers were validated using structure–property correlations and quantum chemical calculations. The literature results of the equilibrium study of alkylation of EG with isobutene were evaluated and the thermodynamic functions of ethylene glycol tert-butyl ethers were derived. The energetics of alkylation determined according to the “First Law” and the “Second Law” methods agree very well. Some interesting aspects related to the entropy of ethylene glycol tert-butyl ethers were also revealed and discussed.