[Background] Zygosaccharomyces bailii is a dominant strain in Chinese Maotai-flavor liquor spontaneous fermentation. However, the effects of other functional strains on Z. bailii is unclear. [Objective] We studied the effects of three other main strains on Z. bailii by co-culture. [Methods] Z. bailii was separately cultured with Saccharomyces cerevisiae, Lactobacillus buchneri, or Bacillus licheniformis. Biomass, pH, ethanol and flavor compounds were determined during the fermentation. Based on the analysis of phenotypic differences, a comparative transcriptome analysis was used to reveal the fermentation mechanisms of Z. bailii in mixed culture with B. licheniformis. [Results] In mixed cultures, the growth and ethanol production of Z. bailii were inhibited by S. cerevisiae, whereas were not affected by L. buchneri or B. licheniformis. Meanwhile, flavor compounds production of Z. bailii was reduced by S. cerevisiae or L. buchneri, but was promoted by B. licheniformis and among them, alcohols, acids, esters and aldehydes increased by 41%, 36%, 44% and 73%, respectively, compared with those in the Z. bailii single culture. Transcriptome analysis of Z. bailii showed that genes related to the metabolism of carbohydrate and amino acids, were significantly up-regulated (≥2-fold, P<0.05) in mixed culture with B. licheniformis. Flavor compounds mainly derived from the metabolism of carbohydrates and amino acids. Therefore, those up-regulated genes might be beneficial for flavor compounds production of Z. bailii. [Conclusion] Z. bailii produced more favor compounds in the co-culture fermentation with B. licheniformis, including alcohols, acids, esters and aldehydes.