Sheath blight (ShB) disease, instigated by Rhizoctonia solani Kuhn, inflicts a significant economic threat to rice production, trailing closely behind blast. Acknowledging the limited understanding of ShB resistance proteomics in highly resistant germplasm, our study aimed to unravel the proteomic intricacies underlying the interaction between resistant landrace Nizam Shait and R. solani. Utilizing Nizam Shait and BPT-5204 as representatives of ShB resistance and susceptibility, a comparative proteome analysis was performed using Orbitrap-Fusion mass spectrometry. The analysis unveiled 5133 differentially expressed proteins, with 118 significantly upregulated and 172 significantly downregulated at a0.05 p-value. Notably, the 14-3-3 like protein GF-E exhibited the highest upregulation, indicating its pivotal role in the brassinosteroid signaling pathway and defense modulation. Proteins associated with systemic acquired resistance, R gene-mediated resistance, and cell death were downregulated, while those linked to jasmonic acid-induced systemic resistance (JA-ISR) showed notable upregulation, confirming ISR induction in response to ShB infection. Key signaling pathways involved in ShB resistance in Nizam Shait encompassed PTI via JA-ISR, cell wall strengthening, and brassinosteroid and abscisic acid-mediated resistance. Validation of the proteome data through qRT-PCR corroborated the findings, underscoring the significance of this research for future proteome assisted breeding efforts aimed at developing ShB resistant rice varieties.