Fusarium head blight (FHB) threatens global wheat (Triticum aestivum L.) production and food security. Fhb1 confers stable, broad-spectrum resistance to FHB, but the underlying molecular mechanisms are not fully understood. In this study, integrated transcriptomic and proteomic analyses of near-isogenic lines for the Fhb1 locus revealed that Fhb1 coordinates a multi-layered defense network characterized by extensive transcriptome reprogramming and post-transcriptional regulation. The phenylpropanoid pathway emerged as a central downstream module, as Fhb1 coordinately upregulates the expression of genes encoding key enzymes in this pathway, including PHENYLALANINE AMMONIA LYASE (PAL), CINNAMATE 4-HYDROXYLASE (C4H), and 4-COUMARATE-CoA LIGASE (4CL). Gene regulatory network analysis identified the R2R3-MYB transcription factor TaMYB30-B1 as a key regulatory hub. A single nucleotide polymorphism (SNP) in TaMYB30-B1 was significantly associated with FHB resistance across natural wheat populations. This association was more pronounced in the absence of Fhb1. Our findings elucidate the mechanistic basis for Fhb1-mediated resistance and highlight TaMYB30-B1 as a valuable target for improving FHB resistance in wheat breeding programs.