2-(Methoxymethoxy)-butane (SMMB) was synthesized, and its boiling point, density, refractive index, and viscosity were measured in this article. The saturated vapor pressure of pure SMMB was determined, and the Antoine equation parameters were calculated. Isobaric vapor-liquid equilibrium (VLE) data for the binary systems of 2-butanol + 2-(methoxymethoxy)-butane (S-1) and 1-butanol + 2-(methoxymethoxy)-butane (S-2) were measured at 101.3 kPa with a modified Rose still. The thermodynamic consistencies of the two series experimental data were checked and confirmed by the Herington area method and Van Ness differential test. The VLE experimental data were correlated by Wilson, NRTL, and UNIQUAC models to obtain the corresponding binary interaction parameters. The T-x-y diagrams of two systems were obtained. Minimum temperature azeotropes were found at 372.56 and 380.70 K for S-1 and S-2 with compositions of 83.85 mol % (2-butanol) and 26.69 mol % (1-butanol) under 101.3 kPa through experiment and calculation. The calculated values using the Wilson, NRTL, and UNIQUAC models were all in good agreement with the experimental data. The separation process was preliminarily simulated by Aspen Plus, and the simulation results were consistent with the experimental results.