The CALPHAD approach in combination with first-principles calculation was employed to perform a thermodynamic modeling of the Cu-Be system. The experimental phase diagram and thermodynamic data available in the literature was critically reviewed. The enthalpy of formation for the ordered γ (bcc_B2) phase at 0 K was computed via first-principles calculation. In addition to the high temperature disordered bcc_A2 form of Be, there are large homogeneity ranges for bcc_A2 and bcc_B2 from 30 to 50 at.% Be over wide temperature ranges . It is thus a challenge for CALPHAD approach in which all of the bcc lattice stabilities might be modeled with a single Gibbs energy function. A stepwise thermodynamic modeling of the disorder (bcc_A2) and order (bcc_B2) transition was proposed to obtain a set of self-consistent thermodynamic parameters for the Cu-Be system. The calculated phase diagram and thermodynamic properties using the present thermodynamic description are in a satisfactory agreement with the experimental data. The presently proposed strategy is equally valid for the modeling of complex order/disorder transition in other binary systems.