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<i>Fusarium graminearum</i> causes <i>Fusarium</i> head blight (FHB), a devastating disease of wheat. Salicylic acid (SA) is involved in the resistance of wheat to <i>F. graminearum</i>. Cell wall mannoprotein (CWM) is known to trigger defense responses in plants, but its role in the pathogenicity of <i>F. graminearum</i> remains unclear. Here, we characterized <i>FgCWM1</i> (<i>FG05_11315</i>), encoding a CWM in <i>F. graminearum</i>. <i>FgCWM1</i> was highly expressed in wheat spikes by 24 h after initial inoculation and was upregulated by SA. Disruption of <i>FgCWM1</i> (&#916;<i>FgCWM1</i>) reduced mannose and protein accumulation in the fungal cell wall, especially under SA treatment, and resulted in defective fungal cell walls, leading to increased fungal sensitivity to SA. The positive role of <i>FgCWM1</i> in mannose and protein accumulation was confirmed by its expression in <i>Saccharomyces cerevisiae</i>. Compared with wild type (WT), &#916;<i>FgCWM1</i> exhibited reduced pathogenicity toward wheat, but it produced the same amount of deoxynivalenol both in culture and in spikes. Complementation of &#916;<i>FgCWM1</i> with <i>FgCWM1</i> restored the WT phenotype. Localization analyses revealed that FgCWM1 was distributed on the cell wall, consistent with its structural role. Thus, <i>FgCWM1</i> encodes a CWM protein that plays an important role in the cell wall integrity and pathogenicity of <i>F. graminearum</i>.