We engineered Z. mobilis ZM4 to express a recombinant glycosyl hydrolase (GH) from Caulobacter crescentus and subjected it to an adaptation in cellobiose medium. Growth on cellobiose was achieved after a prolonged lag phase in cellobiose medium that induced changes in gene expression and cell composition, including increased expression and secretion of GH. These changes were found to be reversible, i.e. not a genetic adaptation, but could be preserved upon transfer to fresh cellobiose medium. After adaptation to cellobiose, our GH expressing strain was able to convert about 50% of cellobiose to glucose within 24 h and use it for growth and ethanol production. Alternatively, adaptation by growth in sucrose medium also enabled immediate growth of Z. mobilis GH3 on cellobiose. Proteomics analysis of cellobiose- and sucrose-adapted strains revealed upregulation of secretion-, transport-, and outer membrane-related proteins, which may aid secretion of GH into the medium. Changes in the cell envelope may additionally enable entry of cellobiose into the cell periplasm or surface display of GHs.