Proposed a novel fermentation strategy of co-culturing C. acetobutylicum/S. cerevisiae integrated with exogenous acetate addition, to enhance acetone and butanol productions simultaneously. Compared with control group, concentrations of butanol and acetone, as well as acetone/butanol ratio reached high levels of 13.91 g/L, 8.27 g/L and 0.59, respectively; with the increments of 19.6%, 41.1% and 18.0%, when adding the synthetic acetate. On the other hand, the relevant fermentation indexes also reached 14.23 g/L, 8.55 g/L and 0.60, respectively, with the increments of 22.4%, 46.0% and 20.0%, when directly adding the cheaper acetate fermentative supernatant, resulting a reduced raw materials cost and enhanced industrial ABE fermentation feasibility. Results show that the proposed strategy could stimulate secretions of the four amino acids, which were beneficial for C. acetobutylicum survival and butanol synthesis; moderately repress NADH regeneration and reduce the cellular energy load. These led to an enhanced acetone synthesis but without sacrificing butanol production, and entire ABE fermentation performance was significantly improved.