The separation of the ternary nonideal system ethyl acetate (EtAC)/ethanol (EtOH)/water with multiazeotropes is very important since they are always generated in the production process of n-butanol synthesis from ethanol, which is much more difficult due to the formation of the multiazeotrope and distillation boundary. Herein, a systematic conceptual design, optimization, and control approach for ternary extractive distillation of multiazeotrope mixtures EtAC/EtOH/water is proposed. The procedure involves entrainer screening, conceptual design, global optimization, process evaluation, and a robust control strategy. The optimization results demonstrate that the total annual cost, exergy loss, and carbon dioxide emissions of the proposed triple-column extractive distillation are significantly reduced compared with those of the existing process. Dynamic performances illustrate that the improved dual temperature and feedforward control strategy can well handle the three product purities, while two kinds of disturbances (i.e., feed flow rate and composition) are introduced.