Endophytes are microbes that live in plant tissues without substantively harming them selves.They are ubiquitous in most plant species, latently residing in or actively colonizing the tissues.To clarify the effect of endophytic fungus on the growth and resistance to drought of winter wheat at the seedling stage under different water conditions, two wheat varieties, Shannong No. 16 and Shannong No. 22, were used as test materials. The dehydrin wzy2 belonging to the dehydration-responsive encoding gene was detected to master different expression of winter-wheat-related genes under drought stress by using a fluorescence quantitative PCR technique. The growth and development of plant and physiological responses under drought stress were investigated by measuring the related physiological indicators and enzyme activity. The results showed that, compared with ND35 groups treated with the normal water, Chaetomium globosum ND35 could significantly improve root-shoot ratio, proline content, protein content, and malondialdehyde (MDA) content of two wheat varieties in the drought group. The water content and soluble sugar content of leaves were reduced slightly in two wheat varieties. In the drought treatment group, C. globosum ND35 could promote root growth of Shannong No. 16 and increase the plant height of Shannong No. 22. The proline content, soluble sugar content, and catalase (CAT) activity of Shannong No. 16 treated with C. globosum ND35 group were increased more than in the control group, while the MDA was reduced by 9.0%. Proline and CAT activity increased and there was an indistinctive difference in soluble sugar content in Shannong No. 22, while the MDA content was reduced. The relative quantitative expression of wzy2 gene was examined. The results showed that dehydrin gene expression in the two wheat varieties inoculated with C. globosum ND35 was increased significantly, compared with that of the control group. Above all, the endophytic fungus C. globosum ND35 could promote seedling root and plant growth, the wheat could develop into three-leaf stage earlier, and resistance to dehydration was enhanced. In addition, wheat root vigor was improved and resistance to drought was increased. The individual water content, sugar content, and proline content in cells were increased, oxidative damage caused by malondialdehyde was reduced, and the activity of catalase was enhanced, thus improving wheat tolerance to drought stress. The expression of related genes wzy2 in quantity was obviously increased in wheat inoculated with C. globosum ND35, and then the expression of resistance to drought-related proteins was improved. As a result, resistance and adaptability to drought stress were improved in winter wheat plants.