A fluid-lattice theory of fluid mixtures is combined with the Gibbs-DiMarzio approach of zero configurational entropy at glass transition in order to correlate and predict the composition dependence of glass transition temperature, Tg, in one-phase polymer mixtures. Such a combination allows an independent quantitative estimation of the significance to Tg of both equation-of-state terms and chain flexibility terms. The model is tested against experimental data on Tg’s for three polymer mixtures known to be compatible in the complete range of composition. The effect of the various binary parameters on glass transition is discussed along with the effect of chain flexibility change upon mixing. It is shown that chain flexibility terms are predominant in determining Tg. Two possible ways of taking into account chain flexibility change are proposed.