<p>At present, wheat production is increasingly failing to meet the demands of a growing population. Studies have shown that dark septate endophytes (DSE) can promote host growth, providing new insights for promoting wheat growth and improving crop yields. In this study, we screened the growth-promoting DSE strain <i>Paraphoma pye</i> (<i>Pp</i>) and inoculated it into wheat seedlings under conditions of no fertilizer, organic nitrogen fertilizer, and inorganic nitrogen fertilizer (0, Y, and W). In combination with transcriptome sequencing, the growth, physiology, and soil indicators of wheat were studied. The results indicated that <i>Pp</i> generally had a positive effect on wheat growth, and this promoting effect was more pronounced under the fertilized conditions. Under different fertilizer treatments, <i>Pp</i> inoculation showed altered impacts on host growth and transcription analysis, particularly in the expression of genes associated with growth and secondary metabolite synthesis. In addition, the combined application of <i>Pp</i> and organic nitrogen fertilizer significantly increased soil enzyme activity, whereas the combined application of <i>Pp</i> and inorganic nitrogen fertilizer increased the host photosynthetic rate, chlorophyll content and nitrogen accumulation. Furthermore, weighted gene co-expression network analysis revealed that the “MAPK signaling pathway” and “glycosphingolipid biosynthesis pathway” may be the key pathways affecting plant phenotypes under <i>Pp</i>-inorganic fertilizer treatment. Overall, this study contributes to the understanding of the effects of DSE combined with fertilizer on plant growth and provides a feasible approach to better promote wheat growth.</p>